New GEO Series

GSE334490 Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging

Fri, 05 Jun 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing ; Other
Organism : Mus musculus

This SuperSeries is composed of the SubSeries listed below.

GSE334468 Butyrate kinase (Buk) links branched-chain fatty acid biosynthesis, cold adaptation, and pathogenesis in Listeria monocytogenes

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Monzur Chowdhury ; Seto Ogunleye ; Matthew Frank ; Hossam Abdelhamed
Series Type : Expression profiling by high throughput sequencing
Organism : Listeria monocytogenes

The phosphate acetyltransferase Ptb and butyrate kinase Buk constitute a proposed alternative route for short-chain acyl-CoA and branched-chain fatty acid (BCFA) precursor metabolism in Listeria monocytogenes. We constructed in-frame deletion mutants of ptb and buk in L. monocytogenes F2365 and found that Buk, but not Ptb, is required for anteiso-BCFA biosynthesis and cold tolerance. The buk mutant displayed reduced anteiso-BCFAs and a shift in phosphatidylglycerol (PG) composition, indicating substantial membrane remodeling. Functionally, the buk mutant exhibited defects in cell-to-cell spread, intracellular replication, phospholipase activity, LLO production, and in vivo virulence, whereas ptb retained wild-type phenotypes. Transcriptomic profiling revealed coordinated metabolic reprogramming in the buk mutant, characterized by downregulation of branched-chain amino acid (BCAA) biosynthesis and phosphotransferase (PTS) systems, indicating impaired precursor supply and nutrient acquisition, along with compensatory upregulation of central metabolism and redox processes. These findings identify Buk for the first time as a metabolic and virulence determinant in L. monocytogenes.

GSE334220 Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging [old_arch CITE-seq]

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Cristobal F Rivera ; Yasmeen M Farra ; Michele Silvestro ; Steven Medvedovsky ; Jacqueline Matz ; Muhammad Yogi Pratama ; John Vlahos ; Bhama Ramkhelawon ; Chiara Bellini
Series Type : Expression profiling by high throughput sequencing ; Other
Organism : Mus musculus

Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic aorta (ATA) compared to distal segments of the aorta and that collagen content increases in both the medial and adventitial compartments of the ATA during aging. The single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T lymphocyte clusters accumulate in the adventitia, while the activation of mechanosensitive Piezo-1 enhances vasoconstriction and contributes to the overall functional decline of ATA tissues. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.

GSE334216 Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging [young_arch CITE-seq]

Fri, 05 Jun 2026 00:00:00 -0400

GSE334154 Driving tumor-associated macrophages to a CXCL9Hi/SPP1Low phenotype eliminates pancreatic cancer

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Yen T. M. Nguyen ; Marc Pfefferlé ; Juhyun Oh ; Grant G. Simpson ; Sierra A. Walker ; Shingo Noguchi ; Christopher S. Garris ; Riley J. Deutsch Williams ; Pratyaksha Wirapati ; Federico De Stefano ; Marie Goemans ; Rui Dai ; Claudio Vinegoni ; Carlos Fernández del Castillo ; Andrew S. Liss ; Mikael Pittet ; Ralph Weissleder
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, with limited therapeutic options. Recent studies have revealed the complex PDAC microenvironment, which fosters interactions between various cell types that contribute to immunosuppression. Among these, tumor-associated myeloid cells with a CXCL9-low, SPP1-high phenotype are particularly abundant and play a significant role in promoting disease progression. We hypothesized that targeting these cells could reprogram the tumor microenvironment and improve survival outcomes. To test this, we developed a novel myeloid cell-targeting nanoformulation, CANDI470, designed to increase CXCL9 expression and reduce SPP1 levels in tumor-associated myeloid cells. Our results demonstrate that this approach not only enhances immune responses but also leads to remarkable therapeutic efficacy, including cures in murine PDAC models, even when used as a monotherapy. This myeloid cell modulation strategy represents a promising new therapeutic avenue for PDAC, offering hope for improved treatment in this otherwise difficult-to-treat malignancy.

GSE334067 Paired mutation calling and spatial transcriptomics identify cellular neighborhoods associated with neoplastic outcomes in mouse colitis

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Elisa B Moutin ; Giada Giavara ; Filipe C Lourenco ; Nefeli Skoufou-Papoutsaki ; Douglas Winton
Series Type : Other
Organism : Mus musculus

In the progression from Inflammatory Bowel Disease to associated cancer, the clonal mutational landscape shifts from selection of mutations in inflammatory genes to selection for cancer-driver mutations. How prevalence and expansion of either type of mutant clones could be impacted by the cellular environments in which they arise, and how this affects the neoplastic outcome of colitis, remains unknown. Here, we combine in vivo lineage tracing, in silico modelling, mutational profiling and spatial transcriptomics in a mouse model of colitis-associated tumorigenesis to capture clone fates associated with chronic inflammation. We identify epithelial- and immune-enriched neighbourhoods and propose a model in which establishment of a reparative tissue environment facilitates tumour initiation by promoting the selection and expansion of pro-oncogenic clones, reducing the span of inflammation-resistant neighbourhoods containing non-oncogenic clones.

GSE333952 Baseline interferon signaling in monocytes and antibody-mediated innate activation at injection site shape mRNA vaccine reactogenicity [ATAC-seq]

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Natacha Madelon ; Gustavo A Ruiz Buendía ; Arnaud M Didierlaurent
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens

The local and systemic symptoms that follow vaccination -collectively referred to as reactogenicity- are common, yet the mechanisms underlying individual variability remain poorly understood. Through longitudinal immune profiling of vaccinated individuals and mechanistic studies in mice, we identified key immunological determinants of reactogenicity induced by mRNA vaccines. Systemic adverse events were associated with stronger interferon and pro-inflammatory responses following the second dose of COVID-19 vaccine, which were also correlated with the magnitude of the antigen-specific adaptive responses. This heightened inflammation occurred within 24 hours of vaccination and originated primarily from the injection site and was characterized by enhanced recruitment and activation of myeloid cells, particularly monocytes. Two mechanisms contributed to this response: (1) early interferon production by muscle T cells generated after the first dose and (2) FcγR-dependent chemokine induction by antigen-specific antibodies. Consistently, serum antibody levels prior to vaccination correlated positively with reactogenicity. In addition to this local amplification mechanism, variability in reactogenicity was influenced by the baseline immune state, as individuals with a pre-existing interferon-stimulated gene signature in monocytes, detectable at both transcriptomic and epigenetic levels, were more prone to systemic symptoms. Our findings reveal molecular and cellular mechanisms driving vaccine reactogenicity, providing a framework for the design of less reactogenic vaccines.

GSE333878 Comparative transcriptomic analysis of rice under cadmium and selenium nanoparticle treatments

Fri, 05 Jun 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing
Organism : Oryza sativa

This study investigated the role of biosynthesized selenium nanoparticles (SeNPs) derived from Chlorella sorokiniana SZ2-1 in alleviating cadmium (Cd) toxicity in rice (Oryza sativa L. cv. Quan Youde Zhan) under hydroponic conditions.The research focused on evaluating the effects of SeNPs on Cd uptake, translocation, subcellular distribution, selenium speciation, and stress-responsive transcriptional regulation. Rice seedlings were exposed to Cd alone or in combination with different concentrations of SeNPs. Physiological, biochemical, ionomic, transcriptomic, and metabolomic analyses were conducted to elucidate the detoxification mechanisms induced by SeNPs.

GSE333743 Modification of VE-cadherin signalling by ZEB1 in Lymphatic Endothelial Cells

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Nada S Ahmed ; Joseph L Horder ; Charles T Cresswell ; Poppy E Harris ; Amy P Lynch ; Zarah B Tabrizi ; Kathryn R Green ; James H Hallwood ; Anton C Smith ; Michael A Portelli ; Alexander J Fezovich ; Christos Spanos ; David S Gardner ; Alan McIntyre ; Sarah J Storr ; Daniel G Booth ; David O Bates ; Andrew V Benest
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor primarily known for its regulatory roles in epithelial-to-mesenchymal transition (EMT) and cell fate determination. Recent studies suggest that endothelial ZEB1 signalling promotes blood vessel growth and reduces junctional integrity, although the underlying mechanisms remain unclear. Notably, the role of ZEB1 in the lymphatic vasculature is unknown, and the regulation of lymphatic integrity by VE-cadherin remains poorly defined. Here, using an integrated proteomic and transcriptomic approach, we identify ZEB1-dependent signalling pathways associated with cell–cell junction reorganisation in lymphatic endothelial cells (LECs). Loss of ZEB1 reduced VE-cadherin phosphorylation at pY731 and pY685 and was accompanied by decreased monolayer resistance and impedance, together with increased leukocyte transendothelial migration. ZEB1 knockdown also reduced YES tyrosine kinase expression and altered YAP1 expression and junctional localisation, changes that were associated with reduced VE-cadherin phosphorylation. Silencing YAP1 in HDLECs similarly reduced VE-cadherin phosphorylation and impaired barrier integrity, recapitulating aspects of the phenotype observed following ZEB1 knockdown. Collectively, these findings suggest that ZEB1 contributes to lymphatic endothelial barrier maintenance in association with altered YAP1 and YES signalling.

GSE333534 Targeting KRAS in a TRP53/KRAS mouse and organoid model inhibits Barrett Esophagus to Gastroesophageal Adenocarcinoma progression

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Linus Schoemig ; Michael Quante
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The lack of experimental systems that faithfully model the genetic and phenotypic progression from Barrett’s esophagus (BE) to gastroesophageal adenocarcinoma (GEAC) has limited mechanistic discovery and preclinical testing. Here, we report a refined L2-IL-1B based mouse model engineered to capture two hallmark alterations of human GEAC: Trp53 loss and elevated KRAS signalling driven by KRAS amplification, modelled through oncogenic KrasG12D activation. This combinatorial genetic approach accelerates malignant transformation and enables controlled, stage-resolved analysis of carcinogenesis at the gastroesophageal junction (GEJ). Parallel murine and human organoid systems recapitulate these in vivo phenotypes and provide a platform for functional interrogation of KRAS amplification, a frequent but understudied driver in GEAC. Using these organoids as treatment avatars in addition to the mouse model, we demonstrate that KRAS dependent growth is selectively vulnerable to combined SHP2 + MEK1/2 or ERK1/2 inhibition, revealing a therapeutically targetable signalling axis. Together, these integrated in vivo and organoid platforms represent a technical advance for modelling BE progression, dissecting KRAS pathway biology, and evaluating targeted strategies for KRAS amplified GEAC.

GSE333510 Baseline interferon signaling in monocytes and antibody-mediated innate activation at injection site shape mRNA vaccine reactogenicity [NanoString nCounter dataset]

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Natacha Madelon ; Gustavo A Ruiz Buendía ; Arnaud M Didierlaurent
Series Type : Expression profiling by array
Organism : Mus musculus

GSE333438 Inherent tissue homeostasis of the juvenile metaphysis provides a foundation for osteosarcoma development [scRNAseq_p21]

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Masato Saito ; Sho Ohta ; Fumie Nakasuka ; Takuya Yamamoto ; Yasuhiro Yamada
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Osteosarcomas typically arise from the metaphyseal cells of juvenile long bones, in contrast to most cancers that develop in aged individuals. Here, we show that the cyclin-dependent kinase inhibitor p21 is expressed in proliferating osteoblasts within the juvenile metaphysis in response to replication stress. Single-cell RNA sequencing focused on the juvenile metaphysis reveals a hierarchical differentiation trajectory of osteoblast-lineage cells, with active proliferation and DNA damage responses predominantly occurring in immature osteoblasts. We find that proliferation of p21+ osteoblasts is mediated by Hedgehog signaling associated with Indian hedgehog (IHH) expression in the growth plate. Consistently, the number of p21+ osteoblasts is markedly reduced following growth plate maturation or pharmacological inhibition of Hedgehog signaling. Induction of c-Myc—a known driver of replication stress and frequently amplified in early-stage osteosarcoma—enhances osteoblast proliferation specifically in juvenile mice, while concurrently augmenting replication stress responses including p53 activation. This c-Myc-driven proliferation remains dependent on Hedgehog signaling and is not sustained after growth plate maturation. Remarkably, functional inactivation of p53 enables continuous proliferation of c-Myc-induced osteoblasts, independent of IHH expression at the growth plate, leading to rapid and widespread metastasis to the lungs. These findings suggest that intrinsic DNA damage responses to replication stress, together with the spatiotemporal restriction of mitogen signaling, safeguard against oncogenic transformation in osteoblasts. Collectively, we uncover the unappreciated aspects of juvenile metaphyseal tissue homeostasis in mice, which may account for the characteristic age of onset, anatomical specificity, and mutational profile of human osteosarcomas.

GSE333235 Baseline interferon signaling in monocytes and antibody-mediated innate activation at injection site shape mRNA vaccine reactogenicity [human_RNAseq]

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Natacha Madelon ; Gustavo A Ruiz Buendía ; Arnaud M Didierlaurent
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

GSE333230 The Transcription Factor IRF8 drives tumor-specific exhaustion in CD8 T cells

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Marco Ongaro ; Grégory Verdeil ; Jesus Corria-Osorio ; Yi-Chuan Wang
Series Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

T-cell exhaustion is a hallmark of chronic infection and cancer and constitutes a major barrier for successful immunotherapies. In this study, we establish the central role of IRF8 as a transcription factor regulating tumor-induced T cell exhaustion. IRF8 is highly expressed in CD8 T cells in tumors but not during chronic infection, where the Irf8 locus is less accessible. Its expression depends on TCR stimulation but is altered in the presence of type I IFN. Overexpression of IRF8 strongly enforced T cell dysfunction while IRF8 knock-out in tumor specific CD8 T cells reduced TOX expression and ameliorated effector function by increasing IFNγ, GrzB and TNF production, resulting in a better tumor control. By comparing IRF8 to IRF2 and IRF4, we showed that the IRF family display some redundancy in the regulation of T cell exhaustion converging on TOX-dependent programs. Altogether, we established a new role for IRF8 as a tumor specific regulator of T cell function.

GSE330326 NAB2::STAT6 Fusion Proteins Drive Nuclear Condensate Formation and Transcriptional Reprogramming in Solitary Fibrous Tumors

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Yi Li ; Jose L Mondaza-Hernandez ; Gauthami Pulivendala ; Fardous Elsenduny ; Felipe Beckedorff ; Guilherme M Lavezzo ; Farhan Vahdat Azad ; Zikun Zhou ; Jeremy Warren ; Paulina I Trevino ; Clark A Meyer ; David Lombard ; Javier Martin-Broto ; David S Moura ; Heather N Hayenga ; Leonidas Bleris
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens

Solitary fibrous tumor (SFT) is a rare and aggressive sarcoma driven by NAB2::STAT6 gene fusions, yet effective targeted therapies remain unavailable. Here, we report that the NAB2ex4::STAT6ex2 fusion variant forms nuclear condensates via liquid-liquid phase separation (LLPS) in engineered fibroblast models and primary SFT cells. These condensates co-localize with BRD4S and EGR1, key transcriptional regulators, and are functionally active, driving widespread transcriptional reprogramming. Treatment with Mithramycin A, a compound that disrupts EGR1-DNA interactions, dissolves NAB2::STAT6 condensates and reverses their aberrant gene expression and chromatin binding signatures. Our findings uncover a previously unrecognized role for NAB2::STAT6 in condensate-mediated oncogenic signaling and provide a mechanistic rationale for condensate-targeted therapy in SFT.

GSE328294 IBI351, a novel KRASG12C inhibitor, enhances αPD-1 efficacy in KRASG12C mutant lung cancer

Fri, 05 Jun 2026 00:00:00 -0400

Contributor : Shuangli Zhu
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

The clinical benefit of immune checkpoint inhibitor (ICI) treatments in patients with advanced KRAS mutant non-small-cell lung cancer (NSCLC) is limited. Here, we found IBI351, a selective KRASG12C inhibitor, significantly enhanced the efficacy of anti-PD-1 antibody (αPD-1) in inhibiting tumor growth in vitro and in vivo. Mechanistically, IBI351 inhibited STAT3 activity, leading to downregulation of stanniocalcin 1 (STC1). STC1 anchors calreticulin (CRT) to the mitochondrial membrane; its downregulation promoted CRT translocation to the cancer cell surface, increasing the ‘eat me’ signal and enhancing T cell infiltration. In clinical specimens from KRASG12C mutant NSCLC patients treated with PD-1 inhibitors, low STC1 expression correlated with better treatment response and prolonged survival. Together, these findings demonstrate that IBI351 enhances ICI efficacy by suppressing the STAT3-STC1 axis and promoting CRT-mediated phagocytosis, supporting further clinical evaluation of this combination.

GSE327535 Early macrophage immune responses and pathogenic features of an emerging Mycobacterium wolinskyi

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Yuxiao Zhao ; Yiwen Gao ; Shixuan Wei ; Weiwei Sun ; Xiaoli Zhang ; Enhua Sun ; Lili Wang ; Zhihong Wu ; Hongwei Pan ; Wei Li
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Mycobacterium wolinskyi is an emerging rapidly growing mycobacterial species whose pathogenic mechanisms and host response patterns remain poorly understood. In this study, a clinical M. wolinskyi strain, designated QL01, was isolated from an 11-year-old child with a facial skin infection. Whole-genome sequencing revealed multiple features associated with pathogenicity, antimicrobial resistance, and host adaptation, including antimicrobial resistance genes, putative virulence factors, genomic islands, prophages, type VII secretion systems, and mammalian cell entry operons. To investigate the early host response, mouse bone marrow-derived macrophages were infected with M. wolinskyi QL01 and subjected to RNA sequencing. Transcriptomic analysis showed broad induction of inflammatory and immunometabolic programs, with prominent enrichment of the TNF, NF-kappa B, and HIF-1 signaling pathways. These findings provide a genomic and transcriptomic framework for understanding host-pathogen interactions involving M. wolinskyi.

GSE327417 Atlas of human gut-associated lymphoid tissue reveals immunomodulatory interactions of B cells

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Jo Spencer ; Michael Pitcher ; Chiara Dionisi
Series Type : Other ; Expression profiling by high throughput sequencing
Organism : Homo sapiens

Gut-associated lymphoid tissue (GALT) is organized lymphoid tissue that responds chronically to antigens, including whole bacteria, sampled from the gut lumen. The ensuing immunoglobulin A (IgA) plasma cell response disseminates to regulate bacterial populations and to mediate intestinal immune homeostasis. GALT has roles in the development of the innate-like marginal zone B cell population and is also associated with a B cell–mediated contribution to ulcerative colitis (UC) severity and response to therapy. Applying integrated multiomics methodologies, we identified key spatially resolved interactions of B cell subsets including broad regulatory features of double negative 2 (DN2) B cells with potential to maintain homeostasis within microbe-rich mucosa. By contrast, GALT in UC is distorted in composition and spatial distribution of B cell subsets that have altered immunomodulatory potential compared to healthy GALT. Thus, we identify interactions of strategically located B cells as mediators of immunological equilibrium in human gut.

GSE326341 Characterization of a Human Cutaneous Squamous Cell Carcinoma Xenograft Mouse Model

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Giorgia Nasi ; Iris K Gratz
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

To study the biology of immune cell biology (e.g. human cutaneous gamma delta T cell) in human skin tumours, an in vivo SCC xenograft mouse model was established. To closely resemble the human skin microenvironment, human tumour cells were introduced into an engineered human skin on the back of NSG mice. Transcriptome analysis of bulk-RNAseq data generated from biopsies of the xenograft model as well as human skin and tumour was conducted to test which features of the model resemble the situation in humans.

GSE326320 Integrative transcriptomic, network, and genomic analysis of peripheral blood mononuclear cells identifies candidate gene drivers of dupilumab clinical response in atopic dermatitis patients

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Martina Krušič ; Mario Gorenjak ; Uroš Potočnik ; Maruška Marovt
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Atopic dermatitis (AD) is among the most common chronic inflammatory diseases. Due to the heterogeneous presentation of AD, patient response to treatment may differ considerably. Therefore, there is a pressing need for biomarkers that could predict response to biological therapies. In line with this, we aimed to identify blood biomarkers that could predict response in patients treated with dupilumab. The present study applied a multi-stage integrative analytical framework combining transcriptomic profiling, functional enrichment, co-expression network analysis, and genomic variant analysis to identify potential biomarkers. Eighteen dupilumab-naïve patients were enrolled in the transcriptomic analysis, with blood samples collected at baseline and after 16–18 weeks of therapy; five patients were identified as non-responders. Additionally, genotyping was performed in 34 patients. We identified a set of candidate genes (RPL18A, RPS28, FAU, MASTL, AURKA, TAF2, BUB1B, and RNF135) and genomic variants that may reflect underlying biological mechanisms influencing therapeutic response. Finally, our study highlighted potential genes that could predict outcome in patients with AD who are treated with dupilumab. Moreover, our study represents an incremental contribution to existing knowledge and opens new avenues for research that may ultimately lead to personalized medicine.

GSE325982 Systemic and breast chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women (Organoid scRNA-Seq)

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Neil Carleton ; Alexander Chang ; Steffi Oesterreich ; Adrian Lee
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Estrogen receptor positive (ER+) breast cancer, the most common subtype of breast cancer, is an age-related disease, with the peak incidence of diagnosis occurring around age 70 despite low circulating levels of estradiol. Despite the hormone sensitivity of these age-related tumors, our understanding of the interplay between the systemic and local hormonal disposition and chronic inflammaging is limited. We show that aged F344 rats treated with the DMBA/MPA carcinogen develop more tumors at faster rates than their younger counterparts, suggesting that the aged environment accelerates tumor growth. snRNA-seq of the tumors showed broad local immune dysfunction that was associated with circulating chronic inflammation. Across a broad cohort of specimens from patients with ER+ breast cancer and age-matched donors of normal breast tissue, we observe that even with E1-predominant estrogen disposition in the systemic circulation, tumors in older patients upregulate HSD17B7 expression to convert E1 to E2 in the TME. Age-related accumulation of tumor-associated macrophages serve as signaling hubs that integrate the E2 and chemokine-driven chronic inflammatory signaling in the TME, which polarize TAMs towards a CD206+/PD-L1+, immunosuppressive phenotype. Overall, these findings suggest that the host's chronic inflammation and hormonal disposition shape the local tumor microenvironment and are critical contributors to the age-related nature of ER+ breast cancer development and growth.

GSE324360 Deep phenotyping of an ATDC5 in-vitro cartilage model system

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Anna Klawonn ; Stefan Tholen ; Ilona Skatulla ; Chiara M Schröder ; Sebastian J Arnold ; Oliver Schilling ; Miriam Schmidts
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Cartilage is characterized by a highly specialized extracellular matrix (ECM) secreted by chondrocytes and limited self-regenerative capacity. In vivo investigations of chondrogenesis are limited by difficult and traumatic access, especially in humans. While it is known for decades that disturbances of chondrocyte differentiation and changed cartilage ECM composition cause severe phenotypes skeletal phenotypes in vertebrates, a detailed molecular understanding of chondrogenesis and cartilage ECM formation is still missing, especially in the context of human genetic skeletal diseases.

GSE319755 Cytotoxic CD39+ tumor-associated NK cells respond to NKG2A blockade in lung cancer (10x Xenium)

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Wiebke Rackwitz ; Annalena Brüggemann ; Carina A Pawlow ; Evgeny Chichelnitskiy ; Clara Serger ; Alfred Zippelius ; Lavinia Neubert ; Christine Falk
Series Type : Other
Organism : Homo sapiens

Natural killer (NK) cell–targeting immunotherapies are emerging, yet the differentiation and functional states of tumor-infiltrating NK cells remain poorly understood. Using matched single-nucleus RNA and ATAC sequencing of samples from patients with non–small cell lung cancer (NSCLC), we resolved the transcriptional and epigenetic landscape of intratumoral NK cells. We identified two tumor-associated NK (taNK) cell subsets marked by expression of ITGAE (CD103) and ITGA1 (CD49a) that display features of tissue residency and dysfunction while preserving cytotoxic function. Trajectory and regulon analyses revealed an inflammation-driven transition from early granzyme K (GZMK)+ NK cells toward an ENTPD1+ (CD39+) effector state characterized by interferon-stimulated gene (ISG) programs. Functional profiling established CD39+ taNK cells as the dominant cytotoxic NK cell population with superior killing capacity that was further potentiated by NKG2A blockade. This study offers mechanistic insights into NK cell differentiation in NSCLC and establishes CD39+ taNK cells as a targetable effector population for immunotherapy.

GSE313397 Hierarchy of grammar rules for the language of transcriptional activation domains

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : David G Cooper ; Bradley K Broyles ; Caleb A Class ; Tamara Y Erkina ; Alexandre M Erkine
Series Type : Other
Organism : Saccharomyces cerevisiae

Transcriptional activation domains (ADs) of eukaryotic gene activators have remained enigmatic for decades as short, consensus-less, extremely variable amino acid sequences that lack a specific structure and interact fuzzily with an uncertain number of targets. Understanding AD sequence grammar is critical for solving the enigma. Using rational design of AD sequences and high-throughput in vivo experimentation combined with bioinformatic analysis and machine learning, we refined grammar rules for AD sequences, calculated the relative importance of each rule, and linked them to the biochemical features essential for biological function. The key feature – redundant representation in the sequence of aromatic and acidic residues - is consistent with the novel idea that ADs function as acidic-hydrophobic surfactants, which is crucial for understanding eukaryotic gene regulation and the function of intrinsically disordered protein regions.

GSE312198 Transcriptomic differences in Vhl-deficient and wild-type (WT) ventricular cardiac tissue using the Wt1-Cre mouse model (RNA-Seq)

Fri, 05 Jun 2026 00:00:00 -0400

Contributor : Silvia Martin-Puig
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

RNA-seq was performed on ventricular cardiac tissue isolated from Vhl-floxed/Wt1-Cre mice and their WT counterparts. This study aimed to characterize the transcriptomic differences in the heart from mice deficient in Vhl in the Wt1 lineage, with the goal of identifying genes regulated by the HIF signaling patway.

GSE308583 Genome-wide Discovery of lncRNAs in Mucorales Reveals Essential Roles in EDF Biology

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Ghizlane Tahiri ; Carlos Lax ; Hrant Hovhannisyan ; Eusebio Navarro ; Toni Gabaldón ; Francisco Nicolás ; Victoriano Garre
Series Type : Expression profiling by high throughput sequencing
Organism : Rhizopus microsporus

Long non-coding RNAs (lncRNAs) emerged as key regulators across eukaryotes, yet their functions in early-diverging fungal (EDF) pathogens remain largely unknown. Here, we provide the first comprehensive identification and characterization of lncRNAs in the EDF order Mucorales, a threatening and WHO high-priority group of opportunistic human pathogens. In this work, we focus on the two major models of this group: Mucor lusitanicus and the clinically relevant pathogen Rhizopus microsporus. We show that EDF lncRNAs exhibit conserved features, dynamic regulation during host interactions, and integration within critical gene regulatory networks. Despite being distributed preferentially in the inactive compartment of chromatin, we found that their expression is associated with 6mA presence in R. microsporus. Additionally, we also found that the lncRNA can be targeted by both canonical and non-canonical RNA pathways active in these fungi. Comparative genomics revealed a subset of evolutionarily conserved lncRNAs, including two essential lncRNAs for fungal viability (lncRNA2 and lncRNA4). LncRNA4 disruption, even in heterokaryosis, resulted in severely affected growth and filamentation. These results establish lncRNAs as indispensable regulators of fungal physiology and pathogenicity, highlighting their potential as novel antifungal targets.

GSE308536 Identification of highly potent inhibitors capable of blocking VprBP kinase activity and suppressing prostate tumor growth

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Sungmin Kim ; Woojin An
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

VprBP has been recently identified as an oncogenic kinase and a promising drug target in human malignant tumors. Although VprBP can phosphorylate histone H2A and some non-histone proteins, it seems to selectively target specific substrates in a cancer type-dependent manner by an unknown mechanism. Here we report that VprBP is highly expressed in prostate cancer cells and inactivates a group of genes encoding critical regulators of cell growth and proliferation in a manner dependent on its kinase activity toward H2AT120. As an extension of our previous finding of VprBP inhibitor B32B3, we also screened a series of small molecule compounds derived from B32B3 and identified B1486 as a second-generation VprBP inhibitor with much higher efficacy and potency. B1486 is far more effective in blocking VprBP-mediated H2AT120p and reactivating growth regulatory genes, resulting in a significantly lower proliferative capacity of prostate cancer cells. Similarly, B1486 treatment inhibits VprBP kinase activity, modulates H2AT120p-induced gene inactivation, and impairs prostate tumor growth in xenograft mouse models. Together, our findings establish a critical role for VprBP-mediated H2AT120p in oncogenic gene silencing and B1486 as a promising therapeutic strategy for prostate cancer.

GSE306916 Efferocytosis induces proangiogenic function and chromatin remodeling in tumor-associated macrophages [ATAC-seq]

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Roi Balaban ; Ori Moskowitz ; Maiia Levinson ; Noam Ofer ; Alice Raizman ; Gaya Levi Kitron ; Eden Aviv ; Sandra Camargo ; Lihi Goldman ; Aviv Leeman ; Eden Noachas ; Chen Sharon-Yagol ; Amir Giladi ; Merav Cohen
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Mus musculus

Macrophages remove apoptotic cells by efferocytosis during immune-surveillance and in the tumor microenvironment (TME). However, the gradual molecular and epigenetic consequences of efferocytosis on the single macrophage are not thoroughly elucidated. Here we introduce Effero-seq, an approach that captures single-cell transcriptomic changes coupled with lysosomal acidification tracked by pHrodo, thus enabling the dissection of molecular dynamics over time following engulfment. Using apoptotic pHrodo-labeled cells as cargo, we defined the effero-score, a gene program gradually upregulated correlatively with pHrodo intensity. In a murine melanoma model, we found that efferocytosis induces a pro-angiogenic function in macrophages with spatial proximity to vascular niches. Moreover, efferocytosis reprograms chromatin accessibility, leading to attenuated macrophage response to IFNγ. In human uveal melanoma, expression of the effero-score is correlated with poor survival. Effero-seq sheds light on the molecular reprogramming induced by efferocytosis in the TME, opening new avenues for understanding macrophage function and developing targeted treatments.

GSE304741 Cytotoxic CD39+ tumor-associated NK cells respond to NKG2A blockade in lung cancer (10X Multiome)

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Clara Serger ; Lucas Rebuffet ; Michael T Sandholzer ; Eric Vivier ; Andrea Romagnani ; Alfred Zippelius
Series Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencing
Organism : Homo sapiens

GSE300757 Efferocytosis induces proangiogenic function and chromatin remodeling in tumor-associated macrophages

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Roi Balaban ; Ori Moskowitz ; Maiia Levinson ; Noam Ofer ; Alice Raizman ; Gaya Levi Kitron ; Eden Aviv ; Sandra Camargo ; Lihi Goldman ; Aviv Leemann ; Eden Noachas ; Chen Sharon-Yagol ; Amir Giladi ; Merav Cohen
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

GSE300310 Human Endogenous Retroviruses Drive Type-I Interferon Signaling activation in Early Rheumatoid Arthritis

Fri, 05 Jun 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Substantial reactivation of HERVs was observed in both synovial tissues and PBMCs from early RA patients. Differentially expressed HERVs regulate adjacent ISGs expression by providing cis-regulatory elements. Moreover, excessive cytoplasmic HERVs trigger a type I interferon (IFN-I) response through the dsRNA-RIG-I-IRF3-IFN-I axis. Targeting endogenous retroviruses exhibited potential therapeutic benefits in both CIA mouse models and RA patient-derived ex vivo models. Specifically, the IFN-I inducible HERV.MLT2B2, a novel primate-specific retroelement, acts as a key driver of the antiviral gene IFI44L, establishing a positive feedback loop that amplifies IFN-I signaling.

GSE299983 Effect of METTL4 knockout on expression and splicing in HeLa S3 cells [human WT]

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Andrey Buyan ; Anastasiia Bolikhova ; Olga Averina ; Alexander Mazur ; Petr Sergiev
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

In this work we studied the role of U2 snRNA m6A(m)30 modification introduced by METTL4 methyltransferase on a model of METTL4 knockout human cell line. METTL4 gene inactivation resulted in dysregulation of gene expression and alternative splicing, as well as general decrease in splicing speed and accuracy.

GSE299981 Effect of METTL4 knockout on expression and splicing in HeLa S3 cells [Human M4]

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Andrey Buyan ; Anastasiia Bolikhova ; Olga Averina ; Alexander Mazur ; Petr Sergiev
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

GSE299977 Metabolic trade-offs in Neonatal sepsis triggered by TLR4 and TLR1/2 ligands result in unique dysfunctions in neural breathing circuits

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Michele J Alves ; Brigitte M Browe ; Ana C Dias ; Juliet Torres ; Giuliana Zaza ; Suzy Bangudi ; Jessica Blackburn ; Wesley Wang ; Silvio de Araujo Fernandes-Junior ; Paolo Fadda ; Amanda Toland ; Lisa A Baer ; Kristin I Stanford ; Catherine Czeisler ; Alfredo J Garcia 3rd ; Jose J Otero
Series Type : Expression profiling by array
Organism : Mus musculus

Expression of the brainstem tissue and cells in postnatal day 5 pups following sepsis-like model with TLR ligands; TLR4 and TLR1/2
We used gene expression to evaluate the inflammatory pathways activated by either saline (control) LPS or PAM3CSK4 in neonates.

GSE299512 Reconstitution of sex-determination process and testicular environment using mouse pluripotent stem cells

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Hayashi Katsuhiko ; Nakamura Tomonori ; Yoshino Takashi
Series Type : Expression profiling by high throughput sequencing
Organism : Mus

Proper differentiation of gonadal somatic cells is crucial for sex determination and subsequent production of sex hormone and gametes. A proper reconstitution of the process in culture will provide not only an appropriate tool for fully understanding the process but also creation of gametes in culture, so called in vitro gametogenesis. Here, we report reconstitution of testicular gonadal somatic cells using mouse pluripotent stem cells. The reconstitution recapitulated a trajectory of the sex-determination process in vivo and consequently provide cell types forming seminiferous tubules and adjacent interstitial tissues including steroidogenic cells. Importantly, the reconstituted testicular tissue incorporated pluripotent stem cell-derived primordial germ cells and provided an environment sufficient for differentiation of spermatogonial stem cells. These spermatogonial stem cells can propagated in culture while keeping potential to differentiate into spermatozoa capable of full-term development with in vitro fertilization followed by transplantation into surrogate mothers. With this reconstitution system, embryonic tissues are no longer required to obtain male germ stem cells, encouraging application to other mammalian species. This study contributes to deeper understanding sex determination process and to creating an alternative source of male germ line in culture.

GSE299260 Parkinson’s disease microglia induce endogenous α-synuclein pathology in patient specific midbrain organoids.

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Elisa Zuccoli ; Hemry Kurniawan ; Sonia Sabate-Soler ; Alise Zagare ; Isabel Rosety ; Anna-Sophie Zimmermann ; Jens C. Schwamborn
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

The accumulation of misfolded α-synuclein and the loss of dopaminergic neurons are hallmarks of Parkinson’s disease (PD), contributing to the development of synucleinopathies. Although considerable progress has been made in understanding α-synuclein's role in PD pathology, the precise mechanisms involved remain unclear. Human midbrain organoids (hMOs) have emerged as valuable models for studying PD, yet the lack of microglia limits the ability to investigate neuroimmune interactions. Recent studies show that integrating microglia into hMOs enhances neuronal maturation and functionality. Here, we generated a human midbrain assembloid model by incorporating iPSC-derived microglia into midbrain organoids from healthy control individuals and a PD patient carrying the SNCA triplication (3xSNCA) mutation. Our results show that 3xSNCA microglia alone are sufficient to induce early, endogenous formation of phosphorylated α-synuclein (pS129) pathology in the absence of exogenous fibril seeding. This PD-pathology emerged as early as day 50 of culture and was not observed in models lacking microglia. These findings highlight a critical role for patient-derived microglia in driving α-synuclein pathology and provide a physiologically relevant platform for studying early neuroimmune mechanisms in PD and testing potential therapeutic strategies.

GSE299045 Arabidopsis aneuploidy mutant C30-81-as6, possesses enormous variations in multiple phenotypic characteristics

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Asanga Deshappriya Nagalla ; Kotaro Ishii ; Tomonari Hirano ; Sumie Ohbu ; Yuki Shirakawa ; Yusuke Kazama ; Tomoko Abe
Series Type : Expression profiling by high throughput sequencing
Organism : Arabidopsis thaliana

The mutant line of C30-81-as6 is an ion beam-generated, Arabidopsis Col-0 based, aneuploid mutant line confirmed by elevated DNA quantity by flow cytometry analysis and microscopic observations of additional chromosome. The mutant shows abnormal leaf shapes, petioless rosette leaves, elevated trichome bases and later flowering phenotypes. A set of candidate causal genes were identified using up and downregulated differentially expressed genes (DEGs) in transcriptome analysis. Gene ontology analysis further supports mutant phenotypic characteristics and provides insights into its functional priorities including promotion of cellular structure and energy production. Meanwhile, the downregulation of senescence-related GO terms validates its extended vegetative phase. The gene density mapping of upregulated DEGs, densely positioned on the long arm of chromosome 2 and phenotype of C30-81-as6 largely resembles Arabidopsis additional chromosome 2 containing aneuploidy mutant.

GSE297565 Inherent tissue homeostasis of the juvenile metaphysis provides a foundation for osteosarcoma development

Fri, 05 Jun 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

This SuperSeries is composed of the SubSeries listed below.

GSE297564 Inherent tissue homeostasis of the juvenile metaphysis provides a foundation for osteosarcoma development [RNA-seq]

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Masato Saito ; Sho Ohta ; Fumie Nakasuka ; Takuya Yamamoto ; Yasuhiro Yamada
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

GSE297558 Inherent tissue homeostasis of the juvenile metaphysis provides a foundation for osteosarcoma development [scRNA-seq]

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Masato Saito ; Sho Ohta ; Fumie Nakasuka ; Takuya Yamamoto ; Yasuhiro Yamada
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

GSE296746 Phenotypic patterns in feline heart failure: a natural model for understanding variable disease severity in humans

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Talitha C. F. Spanjersberg ; Alma H. Hulsman ; Guy C. M. Grinwis ; Babette Janssen ; C. Nina van der Wilt ; Rogier J. A. Veltrop ; Christian Snijders Blok ; Claudia Rozendom ; Paul Besseling ; Jolanda van der Velden ; Pim van der Harst ; Magdalena Harakalova ; Frank G. van Steenbeek
Series Type : Expression profiling by high throughput sequencing
Organism : Felis catus

Cats frequently develop myocardial remodelling, for example, hypertrophic cardiomyopathy, affecting 14.7 percent of domestic cats compared to 0.2 percent of humans, with shared genetic features making them relevant to human disease. Yet features distinguishing clinical outcomes such as heart failure and arterial thromboembolism remain poorly characterized. Using artificial intelligence-based digital pathology and Oxford Nanopore sequencing, we analyzed myocardial tissue from 37 cats grouped by outcome: arterial thromboembolism, congestive heart failure, or no documented cardiac disease. Myocardial fibrosis was significantly higher in cats with arterial thromboembolism, indicating a distinct fibrotic phenotype. Cats with heart failure showed nuclear hypertrophy, while cats with arterial thromboembolism had increased numbers of small, hematoxylin-dense non-myocyte nuclei. Higher fibrosis was associated with downregulation of mitochondrial and cardiac conduction genes, and nuclear size correlated with proteostasis and stress-response pathways. This multimodal framework reveals distinct histological and molecular profiles by outcome, with relevance for translational hypertrophic cardiomyopathy research.

GSE288420 Mitochondrial translation termination, recycling, and rescue in in-frame and out-of-frame contexts

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Taisei Wakigawa ; Mari Mito ; Qi Fang ; Yuzuru Itoh ; Yoichi Shinkai ; Shintaro Iwasaki
Series Type : Other
Organism : Homo sapiens ; Mus musculus

Originating from a bacterial ancestor, the mitochondrial mRNAs have unique characters, including noncanonical stop codons and polycistronic ORFs. However, the molecular mechanisms of how mitochondrial ribosomes terminate the translation and are recycled remain obscure. Harnessing the high-resolution mitochondrial Ribo-Seq and Disome-Seq, here we showed that mtRF1L is a universal release factor for all stop codons, whereas mtRF1 only recognizes AGA/AGG noncanonical stop codons. mtRF1 also terminates mitoribosomes translating out-of-frame ORFs ended with AGA/AGG, explaining the presence of this protein in some vertebrates that do not possess the noncanonical stops in the main ORFs. We also found that mtRRF and mtIF3 require the mitoribosome recycling on stop codons and also reinitiation of internal ORF translation; mitoribosomes stalled at start codons are major substrates of rescue factors of ICT1, mtRF-R, and mtRES1; HEMK1-methylation of release factors enhances the termination reaction on the stop codons. Our results provide an overview of the dynamics of mitoribosomes ending protein synthesis.

GSE276760 Systemic and breast chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women (All Samples; Human and Rat)

Fri, 05 Jun 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing ; Other
Organism : Homo sapiens ; Rattus norvegicus

This SuperSeries is composed of the SubSeries listed below.

GSE276759 Systemic and breast chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women (Rat WES)

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Neil Carleton ; Sanghoon Lee ; Steffi Oestereich ; Adrian Lee
Series Type : Other
Organism : Rattus norvegicus

Estrogen receptor positive (ER+) breast cancer, the most common subtype of breast cancer, is an age-related disease, with the peak incidence of diagnosis occurring around age 70 despite low circulating levels of estradiol. Despite the hormone sensitivity of these age-related tumors, our understanding of the interplay between the systemic and local hormonal disposition and chronic inflammaging is limited. We show that aged F344 rats treated with the DMBA/MPA carcinogen develop more tumors at faster rates than their younger counterparts, suggesting that the aged environment accelerates tumor growth. snRNA-seq of the tumors showed broad local immune dysfunction that was associated with circulating chronic inflammation. Across a broad cohort of specimens from patients with ER+ breast cancer and age-matched donors of normal breast tissue, we observe that even with E1-predominant estrogen disposition in the systemic circulation, tumors in older patients upregulate HSD17B7 expression to convert E1 to E2 in the TME. Age-related accumulation of tumor-associated macrophages serve as signaling hubs that integrate the E2 and chemokine-driven chronic inflammatory signaling in the TME, which polarize TAMs towards a CD206+/PD-L1+, immunosuppressive phenotype. Overall, these findings suggest that the host’s chronic inflammation and hormonal disposition shape the local tumor microenvironment and are critical contributors to the age-related nature of ER+ breast cancer development and growth.

GSE276758 Systemic and breast chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women (Rat snRNA-Seq)

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Neil Carleton ; Sanghoon Lee ; Steffi Oestereich ; Adrian Lee
Series Type : Expression profiling by high throughput sequencing
Organism : Rattus norvegicus

Estrogen receptor positive (ER+) breast cancer, the most common subtype of breast cancer, is an age-related disease, with the peak incidence of diagnosis occurring around age 70 despite low circulating levels of estradiol. Despite the hormone sensitivity of these age-related tumors, our understanding of the interplay between the systemic and local hormonal disposition and chronic inflammaging is limited. We show that aged F344 rats treated with the DMBA/MPA carcinogen develop more tumors at faster rates than their younger counterparts, suggesting that the aged environment accelerates tumor growth. snRNA-seq of the tumors showed broad local immune dysfunction that was associated with circulating chronic inflammation. Across a broad cohort of specimens from patients with ER+ breast cancer and age-matched donors of normal breast tissue, we observe that even with E1-predominant estrogen disposition in the systemic circulation, tumors in older patients upregulate HSD17B7 expression to convert E1 to E2 in the TME. Age-related accumulation of tumor-associated macrophages serve as signaling hubs that integrate the E2 and chemokine-driven chronic inflammatory signaling in the TME, which polarize TAMs towards a CD206+/PD-L1+, immunosuppressive phenotype. Overall, these findings suggest that the host’s chronic inflammation and hormonal disposition shape the local tumor microenvironment and are critical contributors to the age-related nature of ER+ breast cancer development and growth.

GSE276757 Systemic and breast chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women (Rat Bulk RNA-Seq)

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Neil Carleton ; Sanghoon Lee ; Steffi Oestereich ; Adrian Lee
Series Type : Expression profiling by high throughput sequencing
Organism : Rattus norvegicus

Estrogen receptor positive (ER+) breast cancer, the most common subtype of breast cancer, is an age-related disease, with the peak incidence of diagnosis occurring around age 70 despite low circulating levels of estradiol. Despite the hormone sensitivity of these age-related tumors, our understanding of the interplay between the systemic and local hormonal disposition and chronic inflammaging is limited. We show that aged F344 rats treated with the DMBA/MPA carcinogen develop more tumors at faster rates than their younger counterparts, suggesting that the aged environment accelerates tumor growth. snRNA-seq of the tumors showed broad local immune dysfunction that was associated with circulating chronic inflammation. Across a broad cohort of specimens from patients with ER+ breast cancer and age-matched donors of normal breast tissue, we observe that even with E1-predominant estrogen disposition in the systemic circulation, tumors in older patients upregulate HSD17B7 expression to convert E1 to E2 in the TME. Age-related accumulation of tumor-associated macrophages serve as signaling hubs that integrate the E2 and chemokine-driven chronic inflammatory signaling in the TME, which polarize TAMs towards a CD206+/PD-L1+, immunosuppressive phenotype. Overall, these findings suggest that the host’s chronic inflammation and hormonal disposition shape the local tumor microenvironment and are critical contributors to the age-related nature of ER+ breast cancer development and growth.

GSE276755 Systemic and breast chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women (Human Bulk RNA-Seq)

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Neil Carleton ; Sanghoon Lee ; Steffi Oestereich ; Adrian Lee
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Estrogen receptor positive (ER+) breast cancer, the most common subtype of breast cancer, is an age-related disease, with the peak incidence of diagnosis occurring around age 70 despite low circulating levels of estradiol. Despite the hormone sensitivity of these age-related tumors, our understanding of the interplay between the systemic and local hormonal disposition and chronic inflammaging is limited. We show that aged F344 rats treated with the DMBA/MPA carcinogen develop more tumors at faster rates than their younger counterparts, suggesting that the aged environment accelerates tumor growth. snRNA-seq of the tumors showed broad local immune dysfunction that was associated with circulating chronic inflammation. Across a broad cohort of specimens from patients with ER+ breast cancer and age-matched donors of normal breast tissue, we observe that even with E1-predominant estrogen disposition in the systemic circulation, tumors in older patients upregulate HSD17B7 expression to convert E1 to E2 in the TME. Age-related accumulation of tumor-associated macrophages serve as signaling hubs that integrate the E2 and chemokine-driven chronic inflammatory signaling in the TME, which polarize TAMs towards a CD206+/PD-L1+, immunosuppressive phenotype. Overall, these findings suggest that the host’s chronic inflammation and hormonal disposition shape the local tumor microenvironment and are critical contributors to the age-related nature of ER+ breast cancer development and growth.

GSE249357 The effect of glutamine on EMT and lung cancer metastasis

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Yinrui LEI ; Zilong Geng
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

To investigate the effect of glutamine on lung cancer cell EMT and metastasis, we used TGFbeta to treat A549 cells for 24 hours, which were cultured under glutamine depletion or 0.2 mM or 0.5 mM glutamine. RNA-seq was performed to analyze the EMT signature of A549 cells with or without glutamine.

GSE226737 Systematic metabolome analysis of hematopoietic cells identified uridine as a vital anti-aging factor in hematopoiesis

Fri, 05 Jun 2026 00:00:00 -0400

Contributors : Xiangjun Zeng ; Xiaoqing Li ; Pengxu Qian ; He Huang
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

In this study, we employed immunomagnetic enrichment and fluorescence-activated cell sorting (FACS) to isolate 15 hematopoietic cell types, over 9×10^8 hematopoietic cells from 200 young and 150 aged mice, ranging from HSPCs to mature blood cells. UPLC-MS/MS untargeted analysis identified about 2000 metabolites in each cell population, which contributed to define cell-specific signatures and depict aging landscape of blood cells. We further validated our findings by experimentally screening metabolites delaying senescence and identified uridine as potential regulator to rejuvenate aged HSPCs. To enable public access to our dataset, we have constructed an open-source platform (MetaB, www.XXX.com) for easy data browsing and analysis. Collectively, our study developed a solid reference benchmark for metabolic studies in hematopoietic system and provided additional clarity to the mechanisms underlying hematopoietic aging.