New GEO Series

GSE331104 One-Carbon Cycle and Methylation Potential Regulat Behavioral Alcohol Responses via Glutamatergic Neurons

Tue, 19 May 2026 00:00:00 -0400

Contributors : Daniel R Lathen ; Alexandra Seguin ; Collin B Merrill ; Miguel A Pabon ; Maggie M Chvilicek ; Aylin R Rodan ; Adrian Rothenfluh
Series Type : Expression profiling by high throughput sequencing
Organism : Drosophila melanogaster

Despite the enormous harms of alcohol use disorder (AUD), many mechanisms, as well as effective prevention or treatment strategies, remain elusive. Genetic factors dictate much of AUD risk, which can manifest as increased naïve resistance to alcohol’s intoxicating effects or increased functional tolerance, i.e., brain-mediated increases in resistance upon repeat exposure. The underlying neurobiology of how AUD-associated genes alter these endophenotypes remains poorly understood. Genes implicated in AUDs include ones encoding epigenetic modifiers, such as histone demethylase Kdm3. We previously showed that whole-body and neuronal loss of Kdm3 affect ethanol resistance and tolerance in Drosophila. Here, we investigate the mechanisms of these effects. RNA-seq and pathway analysis on Kdm3KO flies revealed disproportionate upregulation of genes involved in amino acid metabolism, including the 1-carbon pathway. We show that acute amino acid feeding modulates behavioral alcohol responses in a Kdm3-dependent manner. Global manipulation of 1-carbon genes also alters alcohol responses. These phenotypic changes are likely mediated by glycine levels (a substrate of these enzymes) rather than by 1-carbon input. Conversely, neuron-specific manipulations of the methionine cycle change alcohol responses in a pattern that suggests a mechanism via S-adenosyl methionine (SAM), a 1-carbon metabolite that is the universal methyl donor required for epigenetic methylation. Increasing SAM production specifically in glutamatergic neurons decreases alcohol resistance and increases tolerance. Together, these findings reveal distinct mechanisms affecting alcohol responses globally (via glycine) versus neuronally (via SAM), thus revealing a complex but important role of neuronal 1-carbon metabolism in mediating behavior.

GSE331097 The extreme diversity of retinal amacrine cells has deep evolutionary roots [rat]

Tue, 19 May 2026 00:00:00 -0400

Contributors : Tommasini Dario ; Monavarfeshani Aboozar ; Dinesh Vishruth ; Hahn Josh ; Tangeman Jared ; Blackshaw Seth ; Puthussery Teresa ; Sanes Josh ; Shekhar Karthik
Series Type : Expression profiling by high throughput sequencing
Organism : Rattus norvegicus

Amacrine cells (ACs) comprise a heterogeneous class of inhibitory neurons in the vertebrate retina, exhibiting morphological and functional complexity rivaling that of cortical interneurons. Here, we integrate single-cell and single-nucleus transcriptomic atlases from 24 vertebrate species to reconstruct the evolutionary origins of this extreme diversity. We identify 42 orthologous AC types (oACs), most of which exhibit a one-to-one correspondence across amniotes and, in many cases, across vertebrates. While core molecular identities are conserved, AC types vary in abundance and gene expression across species, likely reflecting adaptations to distinct visual ecologies. AC diversity scales with that of retinal ganglion cells (RGCs), indicative of co-evolution. Finally, we suggest that ACs arose from an AC-RGC hybrid precursor, with glycinergic ACs diverging early in vertebrate evolution, followed by a bifurcation between RGCs and GABAergic ACs. Together, these findings establish a unified evolutionary framework for understanding the diversity, development, and function of a class of inhibitory neurons across vertebrates.

GSE331070 Inflammatory reprogramming of immature oligodendrocytes perturbs myelination and neurodevelopment in a dual-hit model of preterm brain injury

Tue, 19 May 2026 00:00:00 -0400

Contributors : Xueling Ma ; Wen Jia ; Xingdao Zhang ; Yuan Shi
Series Type : Expression profiling by high throughput sequencing
Organism : Rattus norvegicus

Background: Preterm infants are highly susceptible to white matter injury, in part due to exposure to perinatal inflammation and/or hypoxia. These insults dis_x0002_rupt oligodendrocyte (OL) lineage maturation, leading to impaired myelination and neurodevelopmental deficits; however, the underlying mechanisms remain incompletely understood.
Methods: A dual-hit rat model was established to recapitulate key features of preterm brain injury. Myelination, behavior, and brain function and structure were assessed. The early developmental trajectory of immature OLs was tracked, and the cells were isolated for transcriptomic profiling.
Results: The dual-hit model exhibited delayed myelination, accompanied by long-term behavioral abnormalities, reduced hippocampal functional connectivity, and decreased hippocampal gray matter volume. A marked surge in immature OL death was observed around postnatal day 9. Transcriptomic profiling at this developmentally vulnerable time point revealed pronounced inflammatory reprogramming within immature OLs.
Conclusions: Perinatal inflammation combined with postnatal hypoxia delays myelination and leads to persistent behavioral and brain structural and functional alterations, with immature OLs loss and inflammatory reprogramming emerging as potential drivers of preterm brain injury.

GSE331053 SRSF3 plays a key role in liver cancer sex disparity by facilitating hepatocyte expression of ERα and FOXA

Tue, 19 May 2026 00:00:00 -0400

Contributors : Lulu Yu ; Masahiko Ajiro ; Vladimir Majerciak ; Zhi-Ming Zheng ; Yafeng He
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens

SRSF3 (SRp20) is an essential RNA splicing factor. By conditional knockout (KO) of Srsf3, we discovered Srsf3 at its physiological level plays a tumor-suppressive role in mouse liver carcinogenesis. Srsf3 KO in hepatocytes led to disrupt sex disparity in the development of DEN-induced liver cancer and resulted in high incidence of liver cancer in both male and female mice. In contrast, Srsf3 is oncogenic in the mouse mammary glands and Srsf3 KO significantly delayed the development of Erbb2 breast cancer. Srsf3 KO significantly increased the expression of transcription factors Sox4, E2f1, and Myc, calcium channel factor Trpv4, and zinc-binding Trim6 in liver cancer, but did not in Erbb2 breast cancer. Srsf3 KO enhanced the expression of glucose transmembrane transporter Mfsd4a and translation initiator Eif4a2 in DEN-induced liver cancer but reduced Mfsd4a and Eif4a2 expression in breast cancer. More importantly, Srsf3 KO led to reduced expression of hepatocyte ERα and transcription factor Foxa family genes essential for sexual dimorphism in liver cancer and their downstream targets leukemia inhibitory factor receptor Lifr and epidermal growth factor receptor Egfr, but increased expression of Myc. We further evidenced that SRSF3 binds to FOXA1 promoter and is responsible for FOXA1 promoter activity and FOXA1 expression in liver cancer cells. Together, our data highlights a new functional paradigm of SRSF3 at its physiological level in tissue context-dependent gene regulation and in facilitating hepatocyte ERα and FOXA1 expression for sex disparity in liver cancer development.

GSE330985 Positive and Negative Selection of abT cells (OT-I and OT-II) in the thymus 2 - scRNA-seq, CITE-seq and TCRab

Tue, 19 May 2026 00:00:00 -0400

Contributors : Melanie Vacchio ; Alexander Clark ; Ian Magill ; David Zemmour ; Christophe Benoist ; Rémy Bosselut
Series Type : Expression profiling by high throughput sequencing ; Other
Organism : Mus musculus

This study is part of the immgenT Open Source Project, specifically IGT59, which characterizes activated CD4 and CD8 T cells in the spleen and brain during Toxoplasma gondii infection at 9 dpi (peak infection in the spleen) and 23 dpi (chronic phase with brain cysts). Splenocytes from uninfected controls were also profiled. It includes a spleen control at baseline (6-8-week-old C57BL/6J mouse).

GSE330973 Long-term effects of sperm cryopreservation on zebrafish (Danio rerio) offspring

Tue, 19 May 2026 00:00:00 -0400

Contributors : Xinqing Cai ; Jiamin Wang ; Hongkuan Song ; Xiaohui Chen ; Junfang Zhang ; Bingshe Han
Series Type : Expression profiling by high throughput sequencing
Organism : Danio rerio

Sperm cryopreservation is widely used in zebrafish conservation, but its long-term impacts on offspring impacts remains unclear. This study aims to evaluate whether cryopreservation of zebrafish sperm affects the metabolism of adult offspring. Adult zebrafish generated from cryopreserved sperm are compared to those from fresh sperm. Liver samples are subjected to sequencingto assess changes in potential functional pathways. The results will provide insights into the long-term impact of gamete cryopreservation on offspring metabolism.

GSE330970 SlWRKY2 orchestrates cold tolerance via phytochromes interaction and SlPIF4 stabilization in tomato

Tue, 19 May 2026 00:00:00 -0400

Contributors : Jiachen Hong ; Xiujuan Wang ; Xin Liu ; Xinjie Sun ; Hannah R Thomas ; Jingquan Yu ; Huijia Kang ; Yanhong Zhou
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Solanum lycopersicum

Plants orchestrate stress responses through the integration of light and temperature signals, yet the molecular mechanisms involved in this crosstalk are incompletely elucidated. Here, we identify the transcription factor SlWRKY2 as a critical hub linking phytochrome-mediated light perception with cold stress adaptation in tomato (Solanum lycopersicum). Under cold stress, low red/far-red light ratios significantly induce SlWRKY2 expression and protein accumulation, with phytochrome B (SlphyB) repressing and SlphyA promoting this process. Genetic analyses confirm that SlWRKY2 functions downstream of SlphyB and SlphyA, physically interacts with both SlphyB1 and SlphyA, and acts in a regulatory module where SlphyB negatively regulates cold tolerance while SlphyA exerts a positive effect. Moreover, both cold stress and light signals promote the formation of SlWRKY2 condensates consistent with liquid-liquid phase separation (LLPS). Functionally, SlWRKY2 directly interacts with and stabilizes the light-signaling regulator PHYTOCHROME-INTERACTING TRANSCRIPTION 4 (SlPIF4). Furthermore, SlWRKY2 directly activates SlPIF4 transcription, and the two factors function synergistically to enhance the expression of SlCBFs, as evidenced by genetic data indicating that SlPIF4 is required for SlWRKY2-dependent cold tolerance. Mechanistically, SlWRKY2 competes with SlphyB1 for interaction with SlPIF4. Our findings reveal the SlphyB1/A-SlWRKY2-SlPIF4 signaling module as a pivotal mechanism underlying light quality-dependent cold adaptation, advancing our understanding of how plants integrate environmental cues while providing mechanistic insights into how plants integrate environmental cues to fine-tune cold adaptation.

GSE302373 Nociceptive innervation limits tertiary lymphoid structures to promote lung cancer

Tue, 19 May 2026 00:00:00 -0400

Contributors : Ya-Hsuan Ho ; Giacomo Bregni ; Paola Peinado ; Leanne Li
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Sensory innervation regulates lung physiology and pathology, but its role in lung cancer is poorly understood. We show that lung adenocarcinoma (LUAD) progression locally amplifies nociceptive sensory innervation and activation, which drives the release of a major sensory neuropeptide, calcitonin gene-related peptide (CGRP). CGRP acts on a subset of macrophages, thereby impairing the recruitment of CXCL13+ fibroblasts and blocking tertiary lymphoid structure (TLS) assembly, a key predictor of LUAD prognosis. Local sensory denervation restores TLS formation, enhances B and T cell-dependent immunity, and suppresses tumor growth. Cigarette smoke extract (CSE) further activates this neural circuit to accelerate LUAD progression. In CSE-exposed animals, pharmacologic CGRP blockade sensitizes tumors to immunotherapy and prolongs survival. Together, our findings uncover a neuroimmune axis linking nociceptive neurons, TLS, and LUAD and identify neurogenic inflammation as a mechanism by which smoking promotes lung tumorigenesis independent of somatic mutagenesis.

GSE297644 Atorvastatin regulates hepatic transcriptome PXR dependently but distinct from pregnenolone 16α-carbonitrile and does not induce PXR-mediated liver steatosis

Tue, 19 May 2026 00:00:00 -0400

Contributors : Heba Nabil ; Jukka Hakkola
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Several drugs induce liver steatosis through pregnane X receptor (PXR)-mediated mechanism. Atorvastatin is a PXR ligand but is still safe even in patients with metabolic dysfunction-associated steatotic liver disease. To reveal differences between atorvastatin and other PXR ligands, we characterized the effect of atorvastatin on PXR-mediated gene regulation and liver steatosis in mice. Mice were treated orally with atorvastatin, a classical PXR ligand pregnenolone 16α-carbonitrile (PCN), or pravastatin, a statin not activating PXR. Atorvastatin treatment was also performed in PXR knockout mice. Analysis of liver transcriptomics after four-day treatment indicated that atorvastatin regulates genes almost exclusively through PXR. Atorvastatin and PCN regulated partially overlapping, but distinct set of genes and Cyp3a11 was not induced by atorvastatin. Pathway analysis indicated that the atorvastatin treatment predominantly induced genes involved in cholesterol synthesis, while PCN affected pathways involved in growth, proliferation, and steatosis. PCN increased nuclear SREBP1 protein level while atorvastatin increased both SREBP1 and SREBP2. In high-fat diet (HFD)-fed mice, 28-day oral treatment with PCN aggravated diet-induced liver steatosis while atorvastatin had no effect. 28-day atorvastatin treatment reduced the hepatic expression of PXR, and its effect on cholesterol synthesis genes disappeared. PCN did not influence PXR expression, and the Cyp3a11 expression remained induced still after 28 days. Among the lipogenic genes studied, Scd1 was the only one significantly induced by PCN after 28-day treatment in the HFD-fed mice. In summary, atorvastatin regulates mouse liver transcriptomics PXR dependently but differently from PCN and represses PXR in long-term treatment in the HFD-fed mice. Unlike PCN, atorvastatin does not promote liver steatosis.

GSE297492 Transcriptomic profiling of monocytes and microglia in WNV encephalitis

Tue, 19 May 2026 00:00:00 -0400

Contributors : Wishart Claire L. ; Sptieri Alanna G. ; King Nicholas JC
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Microglia and monocyte-derived cells are key players in West Nile virus (WNV) encephalitis. We used single-cell RNA sequencing (scRNA-seq) using the Rhapsody system to analyse the functional profiles of these cells in the brain and bone marrow during WNV encephalitis over the course of infection.

GSE297163 Uhrf1 determines osteophyte fate by regulating differentiation of synovial mesenchymal progenitor cells [MBD-seq]

Tue, 19 May 2026 00:00:00 -0400

Contributors : Akihiro Jono ; Yuta Yanagihara ; Hiroshi Sakai ; Noritaka Saeki ; Tatsuhiko Kutsuna ; Tomofumi Kinoshita ; Akiyoshi Uezumi ; Masaki Takao ; Yuuki Imai
Series Type : Methylation profiling by high throughput sequencing
Organism : Homo sapiens

This study investigated the role of Uhrf1 in osteophyte formation, building on previous findings of its role in cartilage proliferation and chondrogenic differentiation. We used mesenchymal progenitor cell-specific Uhrf1 knockout (cKO) mice to evaluate osteophyte development and articular cartilage degeneration 2 and 12 weeks post-DMM (destabilization of the medial meniscus) surgery. Two weeks after DMM, cKO mice exhibited significantly smaller osteophytes with reduced width, area, and maturity scores compared to controls. Twelve weeks after DMM, despite similar maturity scores, osteophytes in cKO mice were still smaller, and articular cartilage degeneration was more severe in cKO. UHRF1 knockdown in human synovial cells led to decreased proliferation and chondrogenic differentiation with less methylated DNA. Integrated analyses with RNA-seq and MBD-seq revealed that UHRF1 deficiency upregulates genes that negatively affect cell development and growth including TORC1 and β-catenin-independent Wnt signaling. Among them, knockdown of NLK rescued chondrogenic differentiation, affected by siUHRF1. These results suggest that Uhrf1 in mesenchymal progenitor cells is essential for early osteophyte formation and chondrogenesis through DNA methylation, at least in part, followed by NLK gene suppression. Osteophytes play a protective role against articular cartilage degeneration in osteoarthritis.

GSE260730 The impact of METTL3 on MDM2 impairs cell cycle homeostasis in podocytes during diabetic kidney diseases

Tue, 19 May 2026 00:00:00 -0400

Contributors : Han Wu ; Ziyang Yu ; Zhouting Han ; Qingjun Pan ; Hongyuan Yu ; Ying Chen ; Li Xu
Series Type : Other
Organism : Homo sapiens

The m6A modification, a prevalent epigenetic change, is implicated in various disease processes. Our previous research has revealed METTL3 abnormal expression in aging kidney tissues, correlating with its role in regulating renal fibrosis. In this study, we aim to create a conditional METTL3 knockout model to delve deeper into its regulatory mechanisms in diabetic kidney disease (DKD).Utilizing a conditional, podocyte-specific METTL3 knockout mouse model induced by STZ and transfected mouse podocytes with siMETTL3 plasmids stimulated by advanced glycation end products (AGEs) in vitro, we aim to investigate potential associations between podocyte mitotic catastrophe, the release of inflammatory factors, and diabetic kidney injury. Our focus extends to unraveling the role of METTL3/IGF2BP2 in m6A modification, particularly through MDM2 degradation.Elevated m6A levels were evident in renal tissues of type I diabetic mice and in cultured mouse podocytes exposed to AGEs, attributed to increased METTL3 expression. Podocyte-specific METTL3 knockdown significantly mitigated podocyte injury in STZ-induced diabetic mice, leading to reduced albuminuria and diminished renal pathology. Mechanistically, METTL3 induces abnormal m6A modifications sites of MDM2, triggering subsequent degradation through IGF2BP2 dependent way. Consequently, this abnormal m6A regulation instigates increased MDM2 expression, activating the Notch signaling pathway, prompting podocyte cell cycle re-entry in diabetic conditions, releasing inflammatory factors, and inducing dedifferentiation of podocytes.The aberrant m6A modification, mediated by METTL3, stands pivotal effect of podocytes during diabetic condition. Targeting m6A via METTL3, the writer enzyme, may offer a potential avenue for treating DKD.