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MYOCD is required for cardiomyocytes induction from human urine cells and fibroblasts through remodeling chromatin [ATAC-seq]

ABSTRACT: Despite direct reprogramming of human cardiac fibroblasts into induced cardiomyocytes (iCM) holds great potential for heart regeneration, the mechanisms are poorly understood. Whether other human somatic cells could be reprogrammed into cardiomyocytes is also unknown. Here, we report human urine cells (hUCs) could be efficiently converted into CM-like cells and the associated chromatin accessibility dynamics (CAD) by assay for transposase accessible chromatin(ATAC)-seq. hUCs transduced by MEF2C, TBX5, MESP1 and MYOCD but without GATA4 expressed multiple cardiac specific genes, exhibited Ca2+ oscillation potential and sarcomeric structures, and contracted synchronously in coculture with mouse CM. Additionally, we found that MYOCD is required for both closing and opening critical loci, mainly by hindering the opening of loci enriched with motifs for the TEAD and AP1 family and promoting the closing of loci enriched with ETS motifs. These changes differe partially from CAD observed during iCM induction from human fibroblasts. Collectively, our study offers one robust platform for iCM generation and insights into mechanisms for iCM fate determination.

ORGANISM(S): Homo sapiens

PROVIDER: GSE179011 | GEO | 2021/06/29

REPOSITORIES: GEO

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MYOCD is required for cardiomyocytes induction from human urine cells and fibroblasts through remodeling chromatin [RNA-seq]

Project description:Despite direct reprogramming of human cardiac fibroblasts into induced cardiomyocytes (iCM) holds great potential for heart regeneration, the mechanisms are poorly understood. Whether other human somatic cells could be reprogrammed into cardiomyocytes is also unknown. Here, we report human urine cells (hUCs) could be efficiently converted into CM-like cells and the associated chromatin accessibility dynamics (CAD) by assay for transposase accessible chromatin(ATAC)-seq. hUCs transduced by MEF2C, TBX5, MESP1 and MYOCD but without GATA4 expressed multiple cardiac specific genes, exhibited Ca2+ oscillation potential and sarcomeric structures, and contracted synchronously in coculture with mouse CM. Additionally, we found that MYOCD is required for both closing and opening critical loci, mainly by hindering the opening of loci enriched with motifs for the TEAD and AP1 family and promoting the closing of loci enriched with ETS motifs. These changes differe partially from CAD observed during iCM induction from human fibroblasts. Collectively, our study offers one robust platform for iCM generation and insights into mechanisms for iCM fate determination.

2021-06-29 | GSE179012 | GEO

Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency [RNA-seq]

Project description:Chemical induction of pluripotency (CIP) is an ideal way to reprogram cell fate, but remains poorly understood. Here we report the development of an efficient CIP protocol and the chromatin accessibility dynamics (CAD) during CIP by ATAC-seq. CIP first reorganizes the somatic genome to an intermediate state that must be resolved by primarily closing loci opened earlier before reaching a pluripotent state with gradual opening of loci enriched with motifs for the OCT/SOX/KLF families. Bromodeoxyuridine, a critical ingredient of CIP, is responsible for both closing and opening critical loci, at least in part by preventing the opening of loci enriched with motifs for the AP1 family and facilitating the opening of loci enriched with SOX/KLF/GATA motifs. Our studies provide the first link between small molecules and nuclear architecture in the context of cell fate decisions.

2018-04-10 | GSE110263 | GEO

Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency [ChIP-seq]

2018-04-10 | GSE110262 | GEO

Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency [ATAC-Seq]

2018-04-10 | GSE110261 | GEO

RNA-Seq of Ctrl, Myocd KO, Mrtfa/b DKO and TKO cardiomyocytes

Project description:To characterize transcriptome changes uopn Myocd KO, Mrtfa/b DKO and Mrtfa/b/Myocd TKO in maturing cardiomyocytes

2022-08-01 | GSE210085 | GEO

Protein interaction networks in the vasculature prioritize genes and pathways underlying coronary artery disease (Whitehead data)

Project description:Population-based association studies have identified many genetic risk loci for coronary artery disease (CAD), but it is often unclear how genes within these loci are linked to CAD. Here, we performed interaction proteomics for 11 CAD-risk genes to map their protein-protein interactions (PPIs) in human vascular cells and elucidate their biological relevance in CAD pathogenesis. The PPI networks contain many protein interactions that are outside of known biology in the vasculature and are enriched for genes involved in immunity-related and arterial-wall-specific mechanisms. Furthermore, several PPI networks derived from smooth muscle cells are significantly enriched for genetic variants associated with CAD and related vascular phenotypes. Finally, our networks identified 61 genes that are found in genetic loci associated with risk of CAD, prioritizing them as the causal candidates within these loci. Together, our results indicate that the PPI networks we have generated are a rich resource for guiding future research into the molecular pathogenesis of CAD.

2023-02-27 | MSV000091373 | MassIVE

Co-Stimulation–Induced AP-1 Activity is Required for Chromatin Opening During T Cell Activation [RNA-seq]

Project description:Activation of T cells is dependent on organized and timely opening and closing of chromatin. We perform ATAC-seq (subseries 1), ChIP-seq (subseries 2), and RNA-seq (subseries 3) at 5, 24, and 60 h of T cell activation with anti-CD3 and -CD28 antibodies in human primary naïve CD4 T cells. We report that chromatin opening at early time points is established by AP-1 transcription factor and associated with transcriptional enhancer identified as risk loci for multiple immune diseases in human naïve CD4 T cells.

2019-10-16 | GSE116697 | GEO

Co-Stimulation–Induced AP-1 Activity is Required for Chromatin Opening During T Cell Activation [ATAC-seq]

2019-10-16 | GSE116696 | GEO

Co-Stimulation–Induced AP-1 Activity is Required for Chromatin Opening During T Cell Activation [ChIP-seq]

2019-10-16 | GSE116695 | GEO

Genome-wide maps of Twist2-binding, MyoD-binding and chromatin state in Twist2-overexpressing Twist2+ cells

Project description:Integrated analysis of genome-wide ChIP-Seq and RNA-Seq data revealed the first dynamic chromatin and transcriptional landscape of Twist2 binding during myogenic differentiation. During differentiation, Twist2 competes with MyoD at shared DNA motifs to direct global gene transcription and repression of the myogenic program. Additionally, TWIST2 shapes the epigenetic landscape to drive chromatin opening at oncogenic loci and chromatin closing at myogenic loci. These epigenetic changes redirect MyoD binding from myogenic genes towards oncogenic, metabolic, and growth genes.

2019-03-08 | GSE127998 | GEO

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