Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming (ATAC-seq)

ABSTRACT: Gata4, Mef2c, Hand2, and Tbx5 (GHMT) can reprogram transduced fibroblasts into induced pacemaker-like myocytes (iPMs), but the underlying mechanisms remain obscure. Here we explored the role of Hand2 in iPM formation by using a combination of transcriptome, genome, and biochemical assays. We found many shared transcriptional signatures between iPMs and endogenous sinoatrial node (SAN), yet key regulatory networks remain missing. We demonstrate that Hand2 augments chromatin accessibility at loci involved in sarcomere organization, electrical coupling, and membrane depolarization. Focusing on an established cardiac Hand2 cistrome, we observe selective reorganization of chromatin accessibility to promote pacemaker-specific gene expression. Moreover, we identify a novel Hand2 cardiac subtype diversity (CSD) domain through biochemical analysis of the N-terminus. By integrating our RNA-seq and ATAC-seq datasets, we highlight desmosome organization as a hallmark feature of iPM formation. Collectively, our results illuminate Hand2-dependent mechanisms that may guide future efforts to rationally improve iPM formation.

ORGANISM(S): Mus musculus

PROVIDER: GSE124336 | GEO | 2019/07/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming (RNA-seq)

Project description:Gata4, Mef2c, Hand2, and Tbx5 (GHMT) can reprogram transduced fibroblasts into induced pacemaker-like myocytes (iPMs), but the underlying mechanisms remain obscure. Here we explored the role of Hand2 in iPM formation by using a combination of transcriptome, genome, and biochemical assays. We found many shared transcriptional signatures between iPMs and endogenous sinoatrial node (SAN), yet key regulatory networks remain missing. We demonstrate that Hand2 augments chromatin accessibility at loci involved in sarcomere organization, electrical coupling, and membrane depolarization. Focusing on an established cardiac Hand2 cistrome, we observe selective reorganization of chromatin accessibility to promote pacemaker-specific gene expression. Moreover, we identify a novel Hand2 cardiac subtype diversity (CSD) domain through biochemical analysis of the N-terminus. By integrating our RNA-seq and ATAC-seq datasets, we highlight desmosome organization as a hallmark feature of iPM formation. Collectively, our results illuminate Hand2-dependent mechanisms that may guide future efforts to rationally improve iPM formation.

2019-07-30 | GSE124337 | GEO

Global gene expression in adult cardiac fibroblasts transduced with cardiac transcription factor

Project description:Four transcription factors, GATA4, Hand2, MEF2C, Tbx5 (GHMT) activated cardiac gene expression in cardiac fibroblasts, suggesting that these factors are able to reprogram fibroblasts toward a cardaic cell fate. Total RNA isolated from adult cardiac fibroblasts transduced with empty retroviral vector or GHMT-retroviruses for 2, and 4 weeks.

2012-04-05 | E-GEOD-37057 | biostudies-arrayexpress

Gene expression profiles of mouse embryonic fibroblasts (MEFs), induced cardiomyocytes (iCMs) and heart.

Project description:Global gene expression patterns of the iCMs shift from a MEF state toward a cardiac-like phenotype by Gata4/Mef2c/Tbx5 (GMT) or GMT/Hand2 (GHMT) transduction at 2 and 4 weeks after transduction (2W, 4W). Hand2 upregulated a panel of cardiac genes and suppressed cell cylce genes during cardiac reprogramming.

2017-09-26 | GSE101578 | GEO

Global gene expression in adult cardiac fibroblasts transduced with cardiac transcription factor

2012-04-06 | GSE37057 | GEO

Dynamics of H3K4me2 during cardiac lineage reprogramming

Project description:During reprogramming of fibroblasts into cardiomyocyte-like cells by overexpression of transcription factors, GATA4, Hand2, Mef2C and Tbx5 (GHMT), H3K4Me2, an active histone code, shifts from fibroblast-exclusive peaks to cardiomyocyte-exclusive peaks. Important cardiac genes are gradually marked by this active histone marker. Mouse embryonic fibroblasts (MEFs) and neonatal mouse ventricular cardiomyocytes (NMVMs) represent fibroblasts and cardiomyocytes, respectively. Chromatins harvested from MEFs infected with retroviruses carrying GHMT at day 3, day 5, day 7 post-viral infection were prepared for immunoprecipitation.

2015-07-28 | E-GEOD-71392 | biostudies-arrayexpress

Analysis of transcriptomes during cardioac reprogramming by RNA-deep Sequencing

Project description:Fibroblasts can be reprogrammed into cardiomyocyte-like cells by overexpressing transcription factors, GATA4, Hand2, Mef2C and Tbx5 (GHMT). A83-01, an inhibitor of ALK4, ALK5 and ALK7 and two microRNA, miR-1 and miR-133 increase the efficiency of cardiac reprogramming. RNA_Seq was performed to anyalyze effects of these factors on gene expression. Total RNAs were prepared from mouse embryonic fibroblasts (MEFs); Reprogramming fibroblasts including MEFs transduced with retroviruses encoding GHMT, MEFs transduced with with retroviruses encoding GHMT plus miR-1 and miR-133 (GHMT2m), MEFs transduced with with retroviruses encoding GHMT2m treated with A83-01, at day 7 after viral transduction; and neonatal mouse cardiomyocytes (NMCMs).

2015-07-28 | E-GEOD-71405 | biostudies-arrayexpress

Transcriptome analysis of the effect of DAPT in GHMT-induced cardiac reprogramming

Project description:The purpose of this experiment is to anlyze the transcriptomic changes associated with Notch inhibition, by DAPT treatment, during cardiac reprogramming mediated by GHMT (Gata4, Hand2, Mef2c anf Tbx5).

2017-03-01 | GSE93585 | GEO

Dynamics of H3K4me2 during cardiac lineage reprogramming

2015-07-28 | GSE71392 | GEO

Akt1/Protein Kinase B Enhances Transcriptional Reprogramming of Fibroblasts to Functional Cardiomyocytes

Project description:Conversion of fibroblasts to functional cardiomyocytes represents a potential approach for restoring cardiac function following myocardial injury, but the technique thus far has been slow and inefficient. To improve the efficiency of reprogramming fibroblasts to cardiac-like myocytes (iCMs) by cardiac transcription factors (Gata4, Hand2, Mef2c, and Tbx5=GHMT), we screened 192 protein kinases and discovered that Akt/protein kinase B dramatically accelerates and amplifies this process. Approximately 50% of reprogrammed fibroblasts displayed spontaneous beating after three weeks of induction by Akt plus GHMT. Furthermore, addition of Akt1 to GHMT evoked a more mature cardiac phenotype for iCMs, as seen by enhanced polynucleation, cellular hypertrophy, gene expression, and metabolic reprogramming. Igf1 and Pi3 kinase acted upstream of Akt, whereas mTORC1 and Foxo3a acted downstream of Akt to influence fibroblast-to-cardiomyocyte reprogramming. These findings provide new insights into the molecular basis of cardiac reprogramming and represent an important step toward further application of this technique.

2015-10-01 | GSE68509 | GEO

Analysis of transcriptomes during cardioac reprogramming by RNA-deep Sequencing

2015-07-28 | GSE71405 | GEO