Effect of TGFb on HASMC phenotype after 7 days of treatment
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE288577 | GEO | 2025/09/01
REPOSITORIES: GEO
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Project description:We find that TGFβ signaling in SMCs induced ACSS2-dependent production of Ac-CoA in a PDK4-dependent manner. TGFb induces SMC contractile phenotype and glycolysis.
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Project description:We find that PDK4 knockdown mimics the effect of TGFb in HASMCs, inducing SMC glycolysis and contractile gene expressions. Wherase, ACSS2 knockdown decreases glycolysis and contractile gene expressions.
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Project description:Unlike other terminally differentiated cell types, vascular SMCs display remarkable phenotypic plasticity. The adult, differentiated state is traditionally defined by expression of well-characterized SMC contractile genes. Extracellular cues, however, can induce contractile SMCs to remodel toward a synthetic state characterized by a spectrum of proliferative, migratory, and inflammatory phenotypes. We used whole-genome expression arrays to to identify genes associated with SMC phenotypic modulation. Experiment Overall Design: Rat aortic SMCs were serum-starved for 72 hours and subsequently treated with either PDGF-BB or its respective vehicle (n=2). RNA samples were hybridzed to Affymetrix arrays with the intent to identify early genes associated with SMC phenotypic modulation.
2009-12-02 | E-GEOD-19106 | biostudies-arrayexpress
Project description:Unlike other terminally differentiated cell types, vascular SMCs display remarkable phenotypic plasticity. The adult, differentiated state is traditionally defined by expression of well-characterized SMC contractile genes. Extracellular cues, however, can induce contractile SMCs to remodel toward a synthetic state characterized by a spectrum of proliferative, migratory, and inflammatory phenotypes. We used whole-genome expression arrays to to identify genes associated with SMC phenotypic modulation.
2009-11-20 | GSE19106 | GEO
Project description:ScRNA-seq analysis revealed that aortic stress induced the transition of SMCs from a primary contractile phenotype to proliferative, extracellular matrix (ECM)-producing, inflammatory, and dying phenotypes. Lineage tracing showed the complete transformation of SMCs to fibroblasts and macrophages. ScATAC-seq analysis indicated that these phenotypic alterations were controlled by chromatin remodeling marked by the reduced chromatin accessibility of contractile genes and the induced chromatin accessibility of genes involved in ECM, inflammation, and cell death. IRF3, a pro-inflammatory transcription factor activated by cytosolic DNA, was identified as a key driver for the transition of aortic SMCs from a contractile phenotype to an inflammatory phenotype. In cultured SMCs, cytosolic DNA signaled through its sensor STING-TBK1 to activate IRF3, which bound and recruited EZH2 to contractile genes to induce repressive H3K27me3 modification and contractile gene suppression. In contrast, dsDNA-STING-IRF3 signaling induced inflammatory gene expression in SMCs. In Sting-/- mice, the aortic stress–induced transition of SMCs into an inflammatory phenotype was prevented, and SMC populations were preserved. Finally, profound SMC phenotypic alterations in diverse directions were detected in human ATAAD tissues.
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Project description:ScRNA-seq analysis revealed that aortic stress induced the transition of SMCs from a primary contractile phenotype to proliferative, extracellular matrix (ECM)-producing, inflammatory, and dying phenotypes. Lineage tracing showed the complete transformation of SMCs to fibroblasts and macrophages. ScATAC-seq analysis indicated that these phenotypic alterations were controlled by chromatin remodeling marked by the reduced chromatin accessibility of contractile genes and the induced chromatin accessibility of genes involved in ECM, inflammation, and cell death. IRF3, a pro-inflammatory transcription factor activated by cytosolic DNA, was identified as a key driver for the transition of aortic SMCs from a contractile phenotype to an inflammatory phenotype. In cultured SMCs, cytosolic DNA signaled through its sensor STING-TBK1 to activate IRF3, which bound and recruited EZH2 to contractile genes to induce repressive H3K27me3 modification and contractile gene suppression. In contrast, dsDNA-STING-IRF3 signaling induced inflammatory gene expression in SMCs. In Sting-/- mice, the aortic stress–induced transition of SMCs into an inflammatory phenotype was prevented, and SMC populations were preserved. Finally, profound SMC phenotypic alterations in diverse directions were detected in human ATAAD tissues.
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2017-05-01 | E-GEOD-76853 | biostudies-arrayexpress
Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and directchum regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation. Genome-wide examination of histone H3 and H4 acetylation, as well as ACSS2 binding, in undifferentiated CAD cells and differentiated CAD neurons; background adjusted by H3 ChIP or Input.
2017-05-01 | E-GEOD-76850 | biostudies-arrayexpress