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。

• Impact of sacubitrilat-cGMP-PRKG1 signaling on microtubule detyrosination in cardiomyocytes
  GSE317137Homo sapiens8 个样本2026-10-28

  Microtubule detyrosination (dTyr-tub) and re-tyrosination (Tyr-tub) on the C-terminal residue of alpha-tubulin are mediated by the vasohibin (VASH)-small vasohibin-binding protein (SVBP) complex and tubulin tyrosine ligase (TTL), respectively. The level of dTyr-tub is elevated in heart failure (HF), and reducing this modification improves cardiac function, suggesting HF therapies may modulate it. We investigated whether components of the angiotensin receptor–neprilysin inhibitor LCZ696 affect dTyr-tub in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and explored the underlying mechanisms. Endothelin-1 (ET1) induced hypertrophy and increased dTyr-tub in wild-type but not in SVBP-deficient hiPSC-CMs and did not further enhance hypertrophy in TTL-deficient hiPSC-CMs. Both sacubitrilat and valsartan blocked ET1-induced hypertrophy, but only sacubitrilat prevented dTyr-tub accumulation. Sacubitrilat modestly stabilised atrial natriuretic peptide in culture medium, increased intracellular guanosine 3',5'-cyclic monophosphate (cGMP), augmented the phosphorylation of vasodilator stimulated phosphoprotein (Ser239), a substrate of cGMP-dependent protein kinase 1 (PRKG1), and lowered dTyr-tub level in hiPSC-CMs. Conversely, PRKG1 inhibition or knockdown increased dTyr-tub level. PRKG1A phosphorylated VASH1-WT but not a phosphomimetic VASH1 (VASH1-7E) in vitro. In addition, VASH1-7E did not interact with microtubules and did induce detyrosination. We overexpressed VASH1-WT, -7E and a dephosphorylated form of VASH1 (VASH1-7A) in newly generated VASH1-deficient hiPSC-CMs. The level of dTyr-tub was lower in VASH1-7E- than in VASH1-WT or VASH1-7A-expressing cells. In conclusion, sacubitrilat reduced dTyr-tub levels via PRKG1 activation and VASH1 phosphorylation, a mechanism that may contribute to the therapeutic benefit of LCZ696 in patients with HF.
• Med1 Deletion Reprograms Dental Epithelium into Primitive Hair-Forming Epidermal Architecture via Trp63 Driven Epigenetic Alterations
  GSE316847Mus musculus1 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
• 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
• Soundwave Priming Enhances the Therapeutic Efficacy of Mesenchymal Stromal Cell–Derived Extracellular Vesicles in Acute Respiratory Distress Syndrome
  GSE316041Mus musculus8 个样本2026-10-28

  Our findings provide a robust model in which the UC-EVs cargo modulated by pFUS priming drives improved mitochondrial energetics, barrier protection, and resolution of inflammation, supporting the translational potential of pUC-EVs.
• 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.
• Bulk RNA-seq atlas of cytokine-polarized murinebone-marrow-derived macrophages (BMDMs) across inflammatory, regulatory, and reparative stimuli
  GSE315641Mus musculus81 个样本2026-10-28

  Macrophages are highly plastic immune cells that adopt diverse functional states in response to local microenvironmental cues. In tissues, they contribute to host defense, maintain homeostasis, and coordinate responses to perturbations such as infection, injury, and inflammation. This functional diversity arises from their ability to integrate signals from cytokines, growth factors, and stromal interactions, particularly during tissue damage when macrophages transition from inflammatory to regulatory and reparative states. Despite increasing recognition of macrophage heterogeneity, most transcriptomic studies of macrophage polarization focus on a limited set of stimuli, providing an incomplete view of the cytokine-driven programs that shape macrophage behavior during inflammation and repair. Key mediators, including IL-4, IL-13, IL-33, IL-6, IL-10, GM-CSF, and TGF-β, induce distinct yet partially overlapping transcriptional responses that give rise to specialized and hybrid macrophage states. However, a systematic comparative analysis of these cytokine-induced programs remains lacking. To address this gap, we performed bulk RNA-sequencing of murine bone marrow–derived macrophages stimulated in vitro with a comprehensive panel of cytokines representing inflammatory, regulatory, and reparative pathways. This dataset enables direct comparison of cytokine-specific transcriptional programs, delineates classical, alternative, and hybrid activation states, and provides a resource for studying the molecular basis of macrophage plasticity.

  扰动筛选细胞图谱
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7
  GSE314741synthetic construct8 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.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [endoBID]
  GSE314423Homo sapiens96 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.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [incellSHAPEPool1]
  GSE314422Homo sapiens4 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.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [invitroSHAPEPool1]
  GSE314421Homo sapiens2 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.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [directRNA]
  GSE314420Homo sapiens7 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.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [invitroSHAPEPool1]
  GSE314419Homo sapiens4 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.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [invitroBIDpool2]
  GSE314391Homo sapiens8 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.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [incellBIDPool1]
  GSE314389Homo sapiens66 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.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [invitroBIDPool1]
  GSE314388Homo sapiens6 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.

  扰动筛选
• RNA sequencing demonstrates alterations in the gene expression profile of HUVECs upon NETs stimulation.
  GSE314216Homo sapiens6 个样本2026-10-28

  RNA sequencing was applied to comprehensively assess changes in the gene expression profile of HUVECs following exposure to control or NETs.
• 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 [NanoString]
  GSE300553Homo sapiens6 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 [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.

  扰动筛选
• 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 [scRNA-Seq]
  GSE292990Mus musculus2 个样本2026-10-28

  To investigate the role of Ptbp3 during reprogramming, scRNA-seq was carried out with RNAs isolated from the reprogramming intermediates transfected with shNC or shPtbp3.

  单细胞
• Alternative splicing plays an important role in fast chemical reprogramming [RNA-Seq]
  GSE292989Mus musculus4 个样本2026-10-28

  To investigate the role of Ptbp3 during reprogramming, deep RNA-seq was carried out with RNAs isolated from the reprogramming intermediates transfected with shNC or shPtbp3.
• 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.
• Effect of stable knockdown of KRT18 on gene expression of SAS cells
  GSE292554Homo sapiens6 个样本2026-10-28

  KRT18 was reported to emerge at invasive front and was correlated to poor prognosis in oral squamous cell carcinoma. We extracted the RNA for sequencing from SAS cells which included that of wild type control groups and of stable KRT18 knockdown groups. From the results of GSEA analysis, the hallmark gene sets of epithelial mesenchymal transition (EMT) in KRT18 knockdown cells was highly suppressed. This implied that the emergence of KRT18 at invasive front of oral squamous cell carcinoma and the behavior of invasiveness of the cancer cells might be correlated to the process of EMT.