PRDM16 controls smooth muscle cell fate in atherosclerosis: Fixed-cell scRNAseq datasets [scRNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1304978 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Vascular smooth muscle cells (SMCs) normally exist in a contractile state but can undergo fate switching to produce a variety of cell phenotypes in response to pathologic stimuli. In atherosclerosis, these phenotypically modulated SMCs play a critical role in determining plaque composition and the risk of major adverse cardiovascular events. We found that PRDM16, a transcription factor that has been genetically implicated in cardiovascular disease, is highly expressed in arterial SMCs, and downregulated during SMC fate switching in human and mouse atherosclerosis. Deletion of Prdm16 in SMCs of mice activates the synthetic modulation program in arteries under homeostatic conditions. Upon exposure to atherogenic conditions, these mice form strikingly dense, SMC-rich, fibroproliferative plaques that contain few foam cells. Acute deletion of Prdm16 in SMCs triggers a similar fibrotic response, resulting in the formation of collagen-rich lesions with thick fibrous caps – a hallmark of enhanced lesion stability. Reciprocally, ectopic expression of PRDM16 in cultured cells is sufficient to block SMC synthetic processes, including migration, proliferation, and fibrosis. Mechanistically, PRDM16 binds to chromatin and decreases activating histone marks at synthetic genes. Altogether, our results define PRDM16 as a specific gatekeeper of the synthetic SMC switch and reveal that PRDM16 levels in SMCs predetermine atherogenic lesion composition.
2025-08-28 | GSE305277 | GEO
Project description:Vascular smooth muscle cells (SMCs) normally exist in a contractile state but can undergo fate switching to produce a variety of cell phenotypes in response to pathologic stimuli. In atherosclerosis, these phenotypically modulated SMCs play a critical role in determining plaque composition and the risk of major adverse cardiovascular events. We found that PRDM16, a transcription factor that has been genetically implicated in cardiovascular disease, is highly expressed in arterial SMCs, and downregulated during SMC fate switching in human and mouse atherosclerosis. Deletion of Prdm16 in SMCs of mice activates the synthetic modulation program in arteries under homeostatic conditions. Upon exposure to atherogenic conditions, these mice form strikingly dense, SMC-rich, fibroproliferative plaques that contain few foam cells. Acute deletion of Prdm16 in SMCs triggers a similar fibrotic response, resulting in the formation of collagen-rich lesions with thick fibrous caps – a hallmark of enhanced lesion stability. Reciprocally, ectopic expression of PRDM16 in cultured cells is sufficient to block SMC synthetic processes, including migration, proliferation, and fibrosis. Mechanistically, PRDM16 binds to chromatin and decreases activating histone marks at synthetic genes. Altogether, our results define PRDM16 as a specific gatekeeper of the synthetic SMC switch and reveal that PRDM16 levels in SMCs predetermine atherogenic lesion composition.
2025-08-28 | GSE305272 | GEO
Project description:Vascular smooth muscle cells (SMCs) normally exist in a contractile state but can undergo fate switching to produce a variety of cell phenotypes in response to pathologic stimuli. In atherosclerosis, these phenotypically modulated SMCs play a critical role in determining plaque composition and the risk of major adverse cardiovascular events. We found that PRDM16, a transcription factor that has been genetically implicated in cardiovascular disease, is highly expressed in arterial SMCs, and downregulated during SMC fate switching in human and mouse atherosclerosis. Deletion of Prdm16 in SMCs of mice activates the synthetic modulation program in arteries under homeostatic conditions. Upon exposure to atherogenic conditions, these mice form strikingly dense, SMC-rich, fibroproliferative plaques that contain few foam cells. Acute deletion of Prdm16 in SMCs triggers a similar fibrotic response, resulting in the formation of collagen-rich lesions with thick fibrous caps – a hallmark of enhanced lesion stability. Reciprocally, ectopic expression of PRDM16 in cultured cells is sufficient to block SMC synthetic processes, including migration, proliferation, and fibrosis. Mechanistically, PRDM16 binds to chromatin and decreases activating histone marks at synthetic genes. Altogether, our results define PRDM16 as a specific gatekeeper of the synthetic SMC switch and reveal that PRDM16 levels in SMCs predetermine atherogenic lesion composition.
2025-08-28 | GSE305275 | GEO
Project description:PRDM16 controls smooth muscle cell fate in atherosclerosis [RNA-Seq]
| PRJNA1304974 | ENA
Project description:PRDM16 controls smooth muscle cell fate in atherosclerosis [ChIP-Seq]
| PRJNA1304970 | ENA
Project description:Gene expression profile from brown adipose tissues of Prdm16 knockout and wile type mice. Prdm16 is a transcription factor that regulates the thermogenic gene program in brown and beige adipocytes. However, whether Prdm16 is required for the development or physiological function of brown adipose tissue (BAT) in vivo has been unclear. By analyzing mice that selectively lacked Prdm16 in the brown adipose lineage, we found that Prdm16 was dispensable for embryonic BAT development. Brown adipose tissues were collected from Prdm16 knockout and wiletype mice with 4 biological replicates per condition. Experiment was done in two separate batch for 6-week-old and 11-month-old. Extracted RNA was hybridized to Agilent two-color arrays.
2014-04-09 | E-GEOD-55080 | biostudies-arrayexpress
Project description:Prdm16 is a transcription factor that drives a complete program of brown adipocyte differentiation, but the mechanism by which Prdm16 activates gene transcription remains unknown. Utilizing ChIP-seq teqhnique, we found that Prdm16 binds to chromatin at/near many brown fat-selective genes in BAT. Interestingly, Prdm16-deficiency dramatically reduced the binding of Med1 to Prdm16-target sites. Indeed, Prdm16 binds and recruits Med1 to BAT-enriched genes and the loss of Prdm16 caused a fundamental change in chromatin architecture at key BAT-selective genes and also reduced transcirptional activity. Moreover, Prdm16, through its interaction with Med1, defines and regulates the activity of super-enhancers that drive the expression of cell identity genes. Together, these data demonstrate that Prdm16 drives gene transcription by recruiting Med1 to control chromatin architecture and super-enhancers. Brown adipose tissues were collected from Prdm16 knockout and wiletype 9-month-old mice and ChIP-seq was performed for Prdm16, PolII, Med1, and H3K27ac.
2015-02-10 | E-GEOD-63965 | biostudies-arrayexpress
Project description:Mutation of the PRDM16 gene causes human dilated and noncompaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with postnatal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored. This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN.
2023-07-21 | PXD043601 | Pride
Project description:Group 1 -- WT or PRDM16-KO ex vivo murine MLL-AF9 cells, and PRDM16-KO AF9 cells overexpressing either f-PRDM16 or s-PRDM16. Group 2 -- WT or total PRDM16-KO murine HSCs isolated from adult BM. Group 3 -- WT or total PRDM16-KO murine HSCs isolated from fetal liver. Group 4 -- WT or f-PRDM16-KO murine HSCs (expressing s-PRDM16 only) isolated from fetal liver.
2018-06-08 | GSE112860 | GEO
Project description:PRDM16 ChIP was perfomed in control and Prdm16 KO crypts isolated from the duodenum of 6 week old mice 3 days after inducible gene deletion
2020-02-26 | GSE131487 | GEO