GEO 数据集

主题由标题与摘要自动归类；样本量为数据集标注之和，SuperSeries 可能与其 SubSeries 重复计算。

• Development and preclinical evaluation of a decoy DLL4-encoding oncolytic HSV-1 for solid tumors
  GSE334438Homo sapiens12 个样本2026-10-28

  Preclinical and clinical investigation of oncolytic HSV-1 (oHSV) treatment for cancer has indicated increased Notch signaling in tumors after treatment. Since Notch activation often heralds cancer cell stemness, angiogenesis, and invasion, the induction of this pathway after oHSV virotherapy can support tumor growth and limit response to virotherapy. Here, we evaluated the impact of blocking DLL4, a Notch ligand, on virotherapy. Matched tumor biopsies pre- and post-oHSV (CAN-3110, NCT03152318) treatment revealed an induction of DLL4 post-therapy. We observed that expression of a recombinant soluble decoy DLL4 (sDLL4) could block Notch activation in tumor cells. Thus, we engineered an oHSV vector designed to encode for soluble DLL4 (OVsDLL4) to block DLL4-mediated signaling. RNA sequencing and gene set enrichment analysis revealed that, relative to control oHSV, OVsDLL4 blocked Notch and sprouting angiogenesis pathways after treatment. Despite slower virus replication in vitro, OVsDLL4 cytotoxicity remained effective against tumor cells. Transcriptome profiling also indicated a significant dysregulation of metabolic pathways related to oxidative phosphorylation and glutathione metabolism, in accordance with increased oxygen consumption observed by Seahorse analysis in cells expressing sDLL4. OVsDLL4-treated cells further showed increased reactive oxygen species relative to control oHSV-treated cells. Co-culture of infected tumor cells with macrophages revealed that OVsDLL4 treatment educated macrophage gene expression towards an inflammatory polarization. In vivo, the therapeutic efficacy of OVsDLL4 was underscored after treatment of mice bearing different solid tumors resulted in reduced tumor burden and prolonged survival.
• mRNA and miRNA Sequencing Identifies Increased Oxidative Stress Pathways in a Mouse Model of Ethanol Exacerbation of Colitis [mRNA Seq]
  GSE329642Mus musculus24 个样本2026-10-28

  Alcohol consumption has been found to worsen the pathology of colitis. To elucidate the underlying mechanism, we performed both miRNA and mRNA sequencing of the large intestinal epithelial cells derived from a murine model of alcohol and colitis. Male C57BL/6 received Dextran Sulfate Sodium (DSS) for 5 days to induce colitis and gavaged with alcohol (~3g/kg) or water for 3 days. Three hours after the final gavage, the mice were euthanized and colon lengths were measured, followed by epithelial cell isolation. RNA, including miRNA, was isolated from the colonic epithelial cells and sent to Novogene for mRNA and miRNA sequencing. Analysis comparing DSS Ethanol vs Sham Vehicle mice showed 3931 significantly upregulated genes and 3788 significantly downregulated genes. Functional enrichment analysis of GO and KEGG pathways showed enrichment of superoxide anion generation and HIF-1 signaling pathways, both related to oxidative stress. DSS Ethanol compared to DSS Vehicle resulted in 921 significantly upregulated and 1072 significantly downregulated genes (Padj<0.05) with functional enrichment analysis showing the term with the highest fold enrichment was superoxide anion generation. We further confirmed the RNA and protein expression of NOS2, CYBB, and NCF1 which are involved in nitric oxide and superoxide production. miRNA sequencing revealed 84 differentially expressed miRNAs comparing DSS Ethanol to DSS Vehicle. Functional enrichment analysis of predicted targets of these miRNAs also showed enrichment in superoxide anion generation. These results suggest that combined ethanol and DSS exposure may increase the production of reactive oxygen species, which further damages the intestinal lining and potentially contributes to the ethanol exacerbation of colitis
• mRNA and miRNA Sequencing Identifies Increased Oxidative Stress Pathways in a Mouse Model of Ethanol Exacerbation of Colitis
  GSE329630Mus musculus23 个样本2026-10-28

  Alcohol consumption has been found to worsen the pathology of colitis. To elucidate the underlying mechanism, we performed both miRNA and mRNA sequencing of the large intestinal epithelial cells derived from a murine model of alcohol and colitis. Male C57BL/6 received Dextran Sulfate Sodium (DSS) for 5 days to induce colitis and gavaged with alcohol (~3g/kg) or water for 3 days. Three hours after the final gavage, the mice were euthanized and colon lengths were measured, followed by epithelial cell isolation. RNA, including miRNA, was isolated from the colonic epithelial cells and sent to Novogene for mRNA and miRNA sequencing. Analysis comparing DSS Ethanol vs Sham Vehicle mice showed 3931 significantly upregulated genes and 3788 significantly downregulated genes. Functional enrichment analysis of GO and KEGG pathways showed enrichment of superoxide anion generation and HIF-1 signaling pathways, both related to oxidative stress. DSS Ethanol compared to DSS Vehicle resulted in 921 significantly upregulated and 1072 significantly downregulated genes (Padj<0.05) with functional enrichment analysis showing the term with the highest fold enrichment was superoxide anion generation. We further confirmed the RNA and protein expression of NOS2, CYBB, and NCF1 which are involved in nitric oxide and superoxide production. miRNA sequencing revealed 84 differentially expressed miRNAs comparing DSS Ethanol to DSS Vehicle. Functional enrichment analysis of predicted targets of these miRNAs also showed enrichment in superoxide anion generation. These results suggest that combined ethanol and DSS exposure may increase the production of reactive oxygen species, which further damages the intestinal lining and potentially contributes to the ethanol exacerbation of colitis
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [ASO]
  GSE328887Homo sapiens40 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

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• The Circadian Clock controls Hepatic Inflammation in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD)
  GSE326584Mus musculus24 个样本2026-10-28

  The circadian clock dictates time-of-day dependent gene, protein expression, and metabolite levels to ensure liver homeostasis. Circadian misalignment is implicated in the development of various metabolic disorders, but its contribution to the progression of Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) toward Metabolic dysfunction-Associated Steatohepatitis (MASH) remains poorly understood. Here, we aimed to dissect the role of the circadian clock in MASH development. Using an environmental model of chronic circadian misalignment, combined with metabolic and immune phenotyping, single nuclei transcriptomics and lipidomic profiling, we investigated the role of the clock in MASLD development and hepatic inflammation. To dissect the specific contribution of the immune clock, we used a genetic model overexpressing the clock component Rev-erbα in myeloid cells. Chronic circadian misalignment combined with a high-fat, high-sucrose, cholesterol-enriched (HFHSC) diet markedly amplified hepatic inflammation, characterized by the upregulation of pro-inflammatory genes and increased immune cell infiltration, including the expansion of lipid-associated macrophages (LAMs). Although circadian misalignment did not worsen glucose intolerance or hepatic steatosis, it altered hepatic metabolic gene expression, reflecting a broad reprogramming of immune and metabolic pathways. The circadian clock controls both FA profile and inflammatory process, and its misalignment aggravates MASLD by increasing liver inflammation. Targeting circadian regulators such as Rev-erbα in myeloid cells may offer a promising therapeutic avenue for controlling liver inflammation in MASLD.
• ACSS2-Mediated Metabolic-Epigenetic Crosstalk Drives Fulvestrant Resistance and Represents a Novel Therapeutic Target
  GSE319879Homo sapiens12 个样本2026-10-28

  Endocrine therapies target hormone-dependent cancer cells, primarily through estrogen receptor alpha (ERα), expressed in ~70% of breast cancers (ER+). Despite treatment advances, 30-40% of ER+ breast cancer patients experience recurrence and metastasis, with 5-year survival rates of only 31.9%. We validated poor outcomes for liver metastasis patients treated with Fulvestrant (Fulv) using the local Carle Foundation Hospital cohort and examined metabolic pathways in liver metastatic patient-derived xenograft (PDX) models, revealing upregulated lipid and acetyl-CoA production. Our previous work demonstrated that combining Fulv with acetyl-CoA synthase inhibitor (ACSI) targeting Acyl-CoA Synthetase Short Chain Family Member 2 (ACSS2), synergistically reduced ER+ metastatic breast cancer (MBC) cell viability in vitro. Using multiple analytical approaches-isotope tracing, CUT&RUN sequencing, immunofluorescence, western blot, and RNA sequencing-we characterized the effects of acetyl-CoA synthesis inhibition on Fulv-induced alterations. Fulv treatment of MBC cells increased ACSS2 expression and acetate utilization. Isotope tracing revealed that Fulv decreased acetate flux to the TCA cycle while promoting fatty acid synthesis. Importantly, ACSS2 was predominantly nuclear and CUT&RUN sequencing showed that Fulv treatment increased ACSS2 chromatin occupancy and ERα/ACSS2/H3K27ac overlapping sites near genes associated with tumor progression, which was eliminated by combination of ACSI and Fulv. RNA sequencing revealed reduction of Fulv-induced expression of genes involved in cancer cell metabolism and key signaling pathways in cancer with the Fulv+ACSI combination. In a therapy-resistant xenograft model, combining Fulv and ACSI reduced Fulv-dependent increase in metastatic burden. Our findings indicate ACSS2 contributes to endocrine therapy resistance through nuclear acetyl-CoA provision for epigenetic alterations. Targeting these cancer cell adaptations represents a novel therapeutic approach potentially reducing metastasis-related mortality and improving breast cancer treatment outcomes.
• Med1 Deletion Reprograms Dental Epithelium into Primitive Hair-Forming Epidermal Architecture via Trp63 Driven Epigenetic Mechanisms
  GSE316208Mus musculus12 个样本2026-10-28

  Ectodermal fate decisions between tooth enamel and skin hair are governed by transcription factors, epigenetic mechanisms, and tissue architecture. Deletion of the Mediator subunit Med1, which links enhancer activity to transcriptional output, induces a striking lineage conversion characterized by ectopic hair formation in mouse incisors. Here, we define the cellular, transcriptional, and epigenetic mechanisms underlying this process. Single-cell and spatial transcriptomic analyses reveal extensive remodeling of the incisor epithelium following Med1 deletion, whereby dental pre-ameloblasts and SI cells convert into hair germ–like populations resembling ancestral hair-initiating cells while retaining dental identity. Epidermal fate is driven by the master regulator Trp63, enabling hair formation without follicles distinguishing this process from canonical skin hair regeneration. Mechanistically, epigenetic changes occur in which TRP63 co-localized with alternative MED12-containing enhancers to activate itself and downstream epidermal genes. Together, these findings suggest that Med1 loss promotes hair formation through unique reprogramming to an evolutionarily primitive epidermal state rather than direct trans-differentiation to skin epithelium, providing new insights in ectodermal plasticity.

  单细胞空间转录组
• Dual SGLT1 and 2 inhibition with sotagliflozin decreases oxidative stress in mice with hypertrophic cardiomyopathy due to tropomyosin E180G mutation
  GSE315790Mus musculus21 个样本2026-10-28

  Background. Hypertrophic cardiomyopathy (HCM) is associated with mitochondrial dysfunction and oxidative stress. Our goal was to determine the effects of the dual SGLT1 and SGLT2 inhibitor sotagliflozin (SOTA) on myocardial remodeling, diastolic function, mitochondrial gene expression and oxidative stress in mice with HCM due to the tropomyosin E180G mutation (E180G). Methods. Male E180G and non-carrier (NC) mice 7-8 weeks old were randomized to SOTA formulated in the chow (30 mg/kg chow) or control diet (CD) for 8 weeks. Cardiac structure and function were assessed by echocardiography at baseline, and after 4 and 8 weeks of treatment. At 8 weeks mice were sacrificed to assess myocardial histology, RNA expression, oxidative stress and oxidative sulfonylation of sarcoplasmic reticulum calcium ATPase (SERCA). Results. At baseline E180G mice had myocardial hypertrophy, interstitial fibrosis, diastolic dysfunction and atrial enlargement - all of which worsened over the next 8 weeks. In E180G mice treatment with SOTA for 8 weeks prevented further LV hypertrophy and atrial enlargement, decreased interstitial fibrosis and normalized diastolic function. Mitochondrial gene sets were downregulated, and oxidative stress was increased and associated with oxidative sulfonylation of SERCA at C674. SOTA treatment upregulated mitochondrial gene sets and prevented the increases in oxidative stress and SERCA oxidation. Upregulated fibrosis gene sets in E180G hearts were not affected by SOTA. Conclusion. In E180G HCM mice downregulation of mitochondrial gene sets is associated with increased oxidative stress and oxidative modification of SERCA. In E180G hearts, SOTA corrected the HCM phenotype, normalized diastolic function, upregulated mitochondrial gene sets, and decreased oxidative stress and SERCA oxidation. Upregulation of mitochondrial gene sets leading to improved mitochondrial function may improve energetics and decrease oxidative stress. Oxidative stress leads to oxidative modification of SERCA and stimulation of fibrosis pathways which may play a significant role in HCM, and thus provide an opportunity for therapeutic intervention with agents that improve mitochondrial function and/or decrease oxidative stress.
• Electroconductive Patch Promotes Heart Repair by Directing Epicardial Cell Fate towards Endothelial Lineage
  GSE311450Mus musculus10 个样本2026-10-28

  By developing patches whose electroconductivity matches native myocardium (cardiac electroconductivity-matched patches, CemPs), we show that WT1⁺ EPDCs convert into functional endothelial cells within 14 days of MI, and increase infarct vascular density in adult mice.We employed genetic fate-mapping approaches in WT1CreERT2 H11ZsGtd mice to trace the origin of the newly generated endothelial cells, and combined with single-cell transcriptomics further identifies a previously uncharacterized transitional state cells which is voltage-sensitive and commits to the endothelial lineage via TRPC3–Ca²⁺ signaling.This work elucidates the relationship between the electrical conductivity of biomaterials and the endothelial differentiation potential of WT1⁺ EPDCs, clearly defining the cellular origin of electroconductive patch-induced angiogenesis in adult mammals post-MI.

  单细胞
• Mitochondrial ATP production promotes T cell differentiation and function by regulating chromatin accessibility [RNASeq3]
  GSE310052Mus musculus12 个样本2026-10-28

  Immune elimination of chronic infection or cancer requires cytotoxic CD8 T cells that adopt and maintain an effector phenotype. Cytotoxic T cell function is a bioenergetically demanding process and T cells subjected to chronic antigen exposure have compromised effector function despite high rates of glycolysis. Here we report the ability of the short chain fatty acid, D-α-hydroxybutyrate, to act as a signaling molecule that increases mitochondrial ATP production and drives the conversion of proliferating T cells into cytotoxic effector cells. DAHB signaling switches ATP production from glycolysis to fatty acid oxidation, even in glucose-replete media. This conversion suppresses both AMPK phosphorylation and the integrated stress response (ISR) in activated T cells while significantly elevating the level of the phosphagen, phosphocreatine (PCr). Both the PCr bioenergetic reserve and oxidative phosphorylation were required for T cell effector differentiation. DAHB-induction of CD8-effector gene transcription was coupled to bioenergetics by enhanced ATP-dependent remodeling of chromatin accessibility at effector gene loci. DAHB enhanced CD8 T cell antitumor activity both in vitro and in vivo, and DAHB treatment of transferred T cells led to persistent in vivo antitumor effects. Together, these findings link cellular bioenergetics to the regulation of chromatin accessibility and gene expression required to support effector function.
• ACSS2-Mediated Metabolic-Epigenetic Crosstalk Drives Fulvestrant Resistance and Represents a Novel Therapeutic Target [RNA-Seq]
  GSE300550Homo sapiens18 个样本2026-10-28

  Endocrine therapies target hormone-dependent cancer cells, primarily through estrogen receptor alpha (ERα), expressed in ~70% of breast cancers (ER+). Despite treatment advances, 30-40% of ER+ breast cancer patients experience recurrence and metastasis, with 5-year survival rates of only 31.9%. We validated poor outcomes for liver metastasis patients treated with Fulvestrant (Fulv) using the local Carle Foundation Hospital cohort and examined metabolic pathways in liver metastatic patient-derived xenograft (PDX) models, revealing upregulated lipid and acetyl-CoA production. Our previous work demonstrated that combining Fulv with acetyl-CoA synthase inhibitor (ACSI) targeting Acyl-CoA Synthetase Short Chain Family Member 2 (ACSS2), synergistically reduced ER+ metastatic breast cancer (MBC) cell viability in vitro. Using multiple analytical approaches—isotope tracing, CUT&RUN sequencing, immunofluorescence, western blot, and RNA sequencing—we characterized the effects of acetyl-CoA synthesis inhibition on Fulv-induced alterations. Results showed increased ACSS2 expression and acetate utilization with Fulv treatment. Isotope tracing revealed that Fulv decreased acetate flux to the TCA cycle while promoting fatty acid synthesis, though fatty acid synthesis inhibition did not synergize with Fulv. Importantly, ACSS2 was predominantly nuclear for therapy-resistant cells, suggesting epigenetic regulation roles. CUT&RUN sequencing showed Fulv treatment increased global ACSS2 binding sites and ERα/ACSS2/H3K27ac overlapping sites, which combination ACSI+Fulv therapy completely eliminated. RNA sequencing revealed increased cell proliferation gene expression with Fulv treatment. Combination therapy reduced metastatic burden. Our findings indicate ACSS2 contributes to endocrine therapy resistance through nuclear acetyl-CoA provision for epigenetic alterations. Targeting these cancer cell adaptations represents a novel therapeutic approach potentially reducing metastasis-related mortality and improving breast cancer treatment outcomes.
• ACSS2-Mediated Metabolic-Epigenetic Crosstalk Drives Fulvestrant Resistance and Represents a Novel Therapeutic Target [CUT&Run]
  GSE300549Homo sapiens48 个样本2026-10-28

  Endocrine therapies target hormone-dependent cancer cells, primarily through estrogen receptor alpha (ERα), expressed in ~70% of breast cancers (ER+). Despite treatment advances, 30-40% of ER+ breast cancer patients experience recurrence and metastasis, with 5-year survival rates of only 31.9%. We validated poor outcomes for liver metastasis patients treated with Fulvestrant (Fulv) using the local Carle Foundation Hospital cohort and examined metabolic pathways in liver metastatic patient-derived xenograft (PDX) models, revealing upregulated lipid and acetyl-CoA production. Our previous work demonstrated that combining Fulv with acetyl-CoA synthase inhibitor (ACSI) targeting Acyl-CoA Synthetase Short Chain Family Member 2 (ACSS2), synergistically reduced ER+ metastatic breast cancer (MBC) cell viability in vitro. Using multiple analytical approaches—isotope tracing, CUT&RUN sequencing, immunofluorescence, western blot, and RNA sequencing—we characterized the effects of acetyl-CoA synthesis inhibition on Fulv-induced alterations. Results showed increased ACSS2 expression and acetate utilization with Fulv treatment. Isotope tracing revealed that Fulv decreased acetate flux to the TCA cycle while promoting fatty acid synthesis, though fatty acid synthesis inhibition did not synergize with Fulv. Importantly, ACSS2 was predominantly nuclear for therapy-resistant cells, suggesting epigenetic regulation roles. CUT&RUN sequencing showed Fulv treatment increased global ACSS2 binding sites and ERα/ACSS2/H3K27ac overlapping sites, which combination ACSI+Fulv therapy completely eliminated. RNA sequencing revealed increased cell proliferation gene expression with Fulv treatment. Combination therapy reduced metastatic burden. Our findings indicate ACSS2 contributes to endocrine therapy resistance through nuclear acetyl-CoA provision for epigenetic alterations. Targeting these cancer cell adaptations represents a novel therapeutic approach potentially reducing metastasis-related mortality and improving breast cancer treatment outcomes.
• ACSS2-Mediated Metabolic-Epigenetic Crosstalk Drives Fulvestrant Resistance and Represents a Novel Therapeutic Target [ATACSeq]
  GSE300548Homo sapiens12 个样本2026-10-28

  Endocrine therapies target hormone-dependent cancer cells, primarily through estrogen receptor alpha (ERα), expressed in ~70% of breast cancers (ER+). Despite treatment advances, 30-40% of ER+ breast cancer patients experience recurrence and metastasis, with 5-year survival rates of only 31.9%. We validated poor outcomes for liver metastasis patients treated with Fulvestrant (Fulv) using the local Carle Foundation Hospital cohort and examined metabolic pathways in liver metastatic patient-derived xenograft (PDX) models, revealing upregulated lipid and acetyl-CoA production. Our previous work demonstrated that combining Fulv with acetyl-CoA synthase inhibitor (ACSI) targeting Acyl-CoA Synthetase Short Chain Family Member 2 (ACSS2), synergistically reduced ER+ metastatic breast cancer (MBC) cell viability in vitro. Using multiple analytical approaches—isotope tracing, CUT&RUN sequencing, immunofluorescence, western blot, and RNA sequencing—we characterized the effects of acetyl-CoA synthesis inhibition on Fulv-induced alterations. Results showed increased ACSS2 expression and acetate utilization with Fulv treatment. Isotope tracing revealed that Fulv decreased acetate flux to the TCA cycle while promoting fatty acid synthesis, though fatty acid synthesis inhibition did not synergize with Fulv. Importantly, ACSS2 was predominantly nuclear for therapy-resistant cells, suggesting epigenetic regulation roles. CUT&RUN sequencing showed Fulv treatment increased global ACSS2 binding sites and ERα/ACSS2/H3K27ac overlapping sites, which combination ACSI+Fulv therapy completely eliminated. RNA sequencing revealed increased cell proliferation gene expression with Fulv treatment. Combination therapy reduced metastatic burden. Our findings indicate ACSS2 contributes to endocrine therapy resistance through nuclear acetyl-CoA provision for epigenetic alterations. Targeting these cancer cell adaptations represents a novel therapeutic approach potentially reducing metastasis-related mortality and improving breast cancer treatment outcomes.
• RNA sequencing of HeLa cells infected with CHIKV and CHIKV mutant virus
  GSE299154Homo sapiens12 个样本2026-10-28

  The analysis indicates that CHIKV 6K/TF R37S infection leads to changes in genes related to endoplasmic reticulum stress, and KEGG analysis also enriched pathways related to endoplasmic reticulum stress in biological metabolism. Meanwhile, CHIKV TF ΔPBM infection causes changes in genes related to ion transport, and KEGG analysis has enriched pathways related to biological metabolism that are associated with sugar metabolism
• Transcriptional profiling of white-opaque switiching in Candida tropicalis
  GSE298903Candida tropicalis15 个样本2026-10-28

  The fungal human pathobionts Candida albicans and Candida tropicalis exhibit switching between the sterile "white" state and the mating-competent "opaque" state. In C. albicans, extensive differences in gene expression are observed between white and opaque states. Here, we examined the global gene expression programs in C. tropicalis white and opaque states in strain AM2005/0093. We also examined gene expression programs in a second C. tropicalis isolate (ATCC3419 ST-120) that exhibits tristable switching between white, hybrid and opaque states. Our results reveal both similarities and differences between white-opaque programs between the two C. tropicalis strains.
• Transcriptomic Insights into Cleidocranial Dysplasia Pathogenesis in Alveolar Bone Mesenchymal Stem Cells
  GSE297061Homo sapiens16 个样本2026-10-28

  Cleidocranial dysplasia (CCD) is a genetic disorder that primarily impacts skeletal and dental development, often leading to unerupted teeth due to impaired alveolar bone remodeling. This study investigates the transcriptomic profiles of alveolar bone-derived mesenchymal stem cells (aBMSCs) from CCD patients and unaffected controls to elucidate the molecular mechanisms underlying these dental defects. aBMSCs were isolated from two unrelated CCD patients with confirmed RUNX2 variants (c.673C>T, p.(Arg225Trp) and c.739delA, p.(Ser247Valfs*3)) and from 10 controls. Cells were cultured under general and osteogenic conditions. RNA sequencing, qRT-PCR, and bioinformatic analyses were used to assess gene expression profiles and validate key findings.CCDs exhibited significant dysregulation of ECM genes, including downregulation of COL1A1, COL3A1, and COL5A1 during osteogenic differentiation, indicating impaired bone formation. Disruptions in key signaling pathways, such as G protein-coupled receptor and prostaglandin signaling, highlighted broader osteogenic regulatory perturbations. CCDs displayed distinct transcriptional responses to osteogenic induction, with numerous DEGs, but no single gene was consistently dysregulated across all CCD-control comparisons, reflecting inter-individual heterogeneity. Notably, LGR4, PPP1R12B, PTGER2, and PTGS1 were consistently dysregulated in CCD under both basal and osteogenic conditions, with inverse expression relative to controls. These genes may represent key molecular signatures of CCD and contribute to its phenotypic variability. These findings highlight disrupted ECM formation and transcriptional heterogeneity in CCD, reflecting the complex effects of distinct RUNX2 variants. Consistently dysregulated genes, including LGR4, PPP1R12B, PTGER2, and PTGS1, may serve as key markers of impaired osteogenesis and potential therapeutic targets.

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• Transcriptomic Profiling of Primary Tumor, Brain Metastasis, and Normal Brain Tissues of Lung Adenocarcinoma (LUAD)
  GSE293159Homo sapiens12 个样本2026-10-28

  The objective of this sequencing was to investigate the differential molecular characteristics among primary LUAD, brain metastases (BrM), and normal brains. We aim to identify unique signatures and pathways involved in the metastatic progression of LUAD to the brain, potentially uncovering novel targets for therapeutic intervention.
• Alternative splicing plays an important role in fast chemical reprogramming [CUT&Tag]
  GSE292985Mus musculus12 个样本2026-10-28

  To investigate the role of Ptbp3 during reprogramming, CUT&Tag was carried out from the reprogramming intermediates transfected with shNC or shPtbp3.
• Muscles transcriptomic response to exercise
  GSE287162Mus musculus12 个样本2026-10-28

  The main goal of study was to see the transcriptional response to acute exercise in mice . For this the RNA seq was done in WT rest and WT exercise. We then want to reproduce the same result in HDAC3 ko mice and found the same result. Tissues were harvested immediately after the last session. RNA-seq identified that most differentially expressed genes (DEGs, exercise vs. rest) were upregulated upon exercise. We observed similar results in wild-type (WT) mice comparing exercise vs. rest and found that exercise-induced activation is independent of HDAC3, supporting the rationale for our investigation and demonstrate the robustness and reproducibility of the results that exercise-induced activation of our target gene is independent of HDAC3
• RNA-seq analysis after venetoclax and azacitidine treatment in AML cells
  GSE284469Homo sapiens18 个样本2026-10-28

  RNA-seq analysis was performed in three isogenic MOLM-13 acute myeloid leukemia (AML) cell lines (p53 WT/p53 R248Q/p53 KO) to analyze gene expression changes after treatment with venetoclax and azacitidine.
• Lipid nanoparticle-mediated TFEB mRNA delivering for treatment of non-alcoholic fatty liver disease
  GSE283076Mus musculus16 个样本2026-10-28

  Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by excessive lipid accumulation in the liver, often accompanied by obesity and insulin resistance. As the disease progresses, it can lead to non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and even hepatocellular carcinoma. The excessive activation of the mTORC1 complex promotes TFEB phosphorylation, thereby suppressing the TFEB-dependent lysosomal autophagy pathway and contributing to the development of NAFLD. Therefore, pharmacological activation of TFEB may offer a potential therapeutic strategy for NAFLD. However, currently, there is no drug that can directly activate TFEB. While mTORC1 inhibitors can indirectly activate TFEB, their use is limited by systemic side effects. In this study, we utilized lipid nanoparticles (LNP) to deliver TFEB mRNA to the liver. This targeted approach enhanced TFEB expression in hepatic cells, promoted autophagy, and mitigated NAFLD progression in a murine model.
• Effect of YAP and KLF4 overexpression on gene expression of cerebral microvascular endothelial cells [RNA-Seq]
  GSE280201Mus musculus12 个样本2026-10-28

  Our preliminary findings revealed that YAP acts with KLF4. We here report overexpression of YAP and KLF4, either individually or in combination, led to significant changes in the transcriptomic profiles. YAP and KLF4 have substantial overlaps on co-regulation gene, which has a potential synergistic effect on gene expression. Our findings suggest that the co-regulated DEGs play pivotal roles in vascular and cellular processes, highlighting the synergistic effects of YAP and KLF4 on these biological activities.
• CCM2 knockout promotes transcriptional activity of YAP and KLF4 [CUT&Tag]
  GSE280200Mus musculus12 个样本2026-10-28

  CCM2 knockout dramatically increased the number of KLF4 regulatory genes, and similarly, the number of YAP regulatory genes surged. Consistently, the number of genes co-regulated by KLF4 and YAP also increased after CCM2 loss. Upon performing functional analyses of the genes co-regulated by KLF4 and YAP, we found that the genes in WT primary MBMECs were unable to enrich specific signaling pathways, while the genes in Ccm2-knockout primary MBMECs were enriched in several pathways, including SMAD binding, Rho GTPase binding, kinase regulator activity, et al
• Unveiling the role of UPF1-mediated mRNA decay in melanoma tumorigenesis by modulating the miR-101-3p/NANOS1 axis
  GSE267965Homo sapiens20 个样本2026-10-28

  Numerous studies have reported that Up-frameshift protein 1 (UPF1) as a crucial posttranscriptional regulator in nonsense-mediated mRNA decay (NMD), attributing its role to tumorigenesis across various cancers. However, its recently unveiled function in UPF1-mediated mRNA decay (UMD), intricately coordinated with miRNA, remains unexplored in the context of tumorigenesis. Herein, we elucidate the pivotal role of UPF1 in governing melanoma tumorigenesis by modulation of NANOS1 expression via miR-101-3p. Depletion of UPF1 across three melanoma cell lines significantly impaired cell growth, migration, and invasion by cell cycle arrest and disrupted tumor formation in vivo. Through comprehensive RNA-seq and biochemical analyses, we elucidate that attenuation of UPF1 leads to an increase in NANOS1 expression, consequently suppressing melanoma tumorigenesis. Mechanistically, UPF1 orchestrates the destabilization of NANOS1 via UPF1-mediated mRNA decay (UMD) facilitated by miR-101-3p. Intriguingly, our findings highlight a novel protein modification event involving the phosphorylation of ELK1 by the UPF1/miR-101-3p/NANOS1 pathway, as revealed by antibody microarray analysis. Importantly, our study underscores the significance of UPF1 and NANOS1 in regulating melanoma tumorigenesis, even in drug-resistant cell lines and in vivo models including syngeneic and xenograft mouse models. Collectively, these insights shed light on the role of UMD in melanoma tumorigenesis through the UPF1/NANOS1/miR-101-3p axis and unveil potential therapeutic strategies for both primary and drug-resistant melanoma treatment.
• Detailed characterization of the immune response to Epstein-Barr virus in multiple sclerosis and following B cell depleting treatment
  GSE352228Homo sapiens24 个样本2026-10-27

  B-cell-depleting therapies are increasingly used for the treatment of multiple sclerosis (MS). Here, we characterize the impact of BCDT on humoral and cellular immune response to Epstein-Barr virus (EBV) in persons with MS (pwMS). We find that EBV viral load does not differ between pwMS and HC. By contrast, distinct differences are found in both humoral and cellular EBV-specific immunity in MS. EBV-specific antibody titres are increased in pwMS, whereas cellular immunity diverges toward lower CD8+ T cell reactivity against lytic antigens, including BZLF1. Notably, during periods of disease activity, both CD4+ and CD8+ T cell responses to lytic antigens tend to be higher. In addition, BZLF1-specific T cell clones recognizing the peptide RAKFKQLL were the most clonally expanded population in the intrathecal compartment of a pwMS with high CSF T cell counts. BCDT reduces EBV viral load and is associated with pronounced reduction in CD8+ T cell responses to all lytic EBV antigens. These findings delineate distinct alterations in EBV-specific immunity in MS and demonstrate that BCDT modulates both viral load and T cell responses. The data support a potential role for CD8+ T cell clones targeting lytic EBV proteins in MS pathogenesis.
• Transcriptome-wide mapping reveals an RNA-dependent mechanism of platinum cancer drugs. [ptRNAseq_A2780_Fractionation]
  GSE352212Homo sapiens24 个样本2026-10-27

  Clinically used small molecules have been predicted to off-target to RNAs. However, the extent of this interaction is small molecule cancer therapeutics have not been characterized. Here, we screened for anticancer small molecules for their RNA interactions and uncovered widespread RNA off-targeting. Cisplatin was found to be one among the RNA binders. We used it as a model agent to identify the specific transcripts it interacts with. To accomplish this, we developed Plat-RNAseq, a click-chemistry-mediated transcriptome-wide assay. Our results revealed that cisplatin binding was enriched at guanine-rich regions capable of forming RNA G-quadruplexes (rG4s). We found that the recruitment of cisplatin to rG4s partially contributed to its cytotoxicity, revealing a noncanonical mechanism of action for this widely used chemotherapeutic agent. This experiment applied PlatRNA-seq to chromatin-associated, nuclear and cytoplasmic RNA fractions to assess whether platinum binding occurs co-transcriptionally or on mature RNA.
• Transcriptomic analysis of mucosal immunity in mouse lung tissues induced by sequential Sad23L-RSV vaccination
  GSE352070Mus musculus15 个样本2026-10-27

  We performed transcriptomic analysis of lung tissues from BALB/c mice vaccinated with a novel adenovirus-vectored RSV vaccine (Sad23L-RSV) via an intranasal prime/intramuscular boost regimen. Lung tissues were collected at days 0, 2, 7, and 28 after the booster immunization to investigate the molecular mechanisms of durable mucosal immunity.
• Transcriptomics of human fetal microglia infected with HIV-1
  GSE351613Homo sapiens36 个样本2026-10-27

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Transcriptomics of human fetal microglia infected with HIV-1 [V8 RNA-Seq]
  GSE351612Homo sapiens12 个样本2026-10-27

  Microglia act as HIV reservoirs in the brain and contribute to the development of HIV-associated neurocognitive disorders. Understanding the pathobiology of HIV-infected microglia is therefore essential. Here, we examined the transcriptome of primary microglia infected ex vivo with HIV-1. Analyses reveal a significant expression modulation of DNA/cell cycle, cellular stress-related, as well as non-membrane bounded organelle assembly-related genes, and a broad effect on microRNA expression. MicroRNA-23b is identified among upregulated microRNAs in HIV-1-infected microglia, and the downregulated g3bp2 mRNA validated as its target. G3BP2 is a component of stress granules (SGs), which serve as antiviral and proinflammatory platforms. MicroRNA-23b mimics reduce both SG assembly and G3BP2 expression in arsenite (As)-treated monocyte-derived microglial cells (MDMi), and few SGs aggregate in infected MDMi in response to As-mediated stress. MicroRNA-23b inhibitors partially re-establish SG formation and reduce HIV-1 replication and spread. Thus, microRNA-23b induction enables HIV-1 to counter SG assembly in infected microglia, a host response that restricts HIV-1 replication and ensuing neuropathogenesis
• Transcriptomics of human fetal microglia infected with HIV-1 [V6 miRNA-Seq]
  GSE351611Homo sapiens24 个样本2026-10-27

  Microglia act as HIV reservoirs in the brain and contribute to the development of HIV-associated neurocognitive disorders. Understanding the pathobiology of HIV-infected microglia is therefore essential. Here, we examined the transcriptome of primary microglia infected ex vivo with HIV-1. Analyses reveal a significant expression modulation of DNA/cell cycle, cellular stress-related, as well as non-membrane bounded organelle assembly-related genes, and a broad effect on microRNA expression. MicroRNA-23b is identified among upregulated microRNAs in HIV-1-infected microglia, and the downregulated g3bp2 mRNA validated as its target. G3BP2 is a component of stress granules (SGs), which serve as antiviral and proinflammatory platforms. MicroRNA-23b mimics reduce both SG assembly and G3BP2 expression in arsenite (As)-treated monocyte-derived microglial cells (MDMi), and few SGs aggregate in infected MDMi in response to As-mediated stress. MicroRNA-23b inhibitors partially re-establish SG formation and reduce HIV-1 replication and spread. Thus, microRNA-23b induction enables HIV-1 to counter SG assembly in infected microglia, a host response that restricts HIV-1 replication and ensuing neuropathogenesis