Chemical Enhancement of Direct Cardiac Reprogramming In Vitro and In Vivo
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE81809
PROVIDER: PRJNA322596 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3578680.fastq.gz | Fastqsanger.gz | |||
| SRR3578690.fastq.gz | Fastqsanger.gz | |||
| SRR3578700.fastq.gz | Fastqsanger.gz | |||
| SRR3578710.fastq.gz | Fastqsanger.gz | |||
| SRR3578720.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells (iCMs) in situ represents a promising strategy for cardiac regeneration. A combination of three cardiac transcription factors, Gata4, Mef2c and Tbx5 (GMT), can convert fibroblasts into iCMs, albeit with low efficiency in vitro. Here, we screened 5,500 compounds in primary cardiac fibroblasts and found that a combination of the transforming growth factor (TGF)-β inhibitor SB431542 and the WNT inhibitor XAV939 increased reprogramming efficiency eight-fold when added to GMT-overexpressing cardiac fibroblasts. The small-molecules also enhanced the speed and the quality of cell conversion, as we observed beating cells as early as 1 week after reprogramming compared to 6–8 weeks with GMT alone. In vivo, mice exposed to GMT, SB431542, and XAV939 for 2 weeks after myocardial infarction showed significantly improved reprogramming and cardiac function compared to those exposed to only GMT. Human cardiac reprogramming was similarly enhanced upon TGF-b and WNT inhibition and was achieved most efficiently with GMT plus Myocardin. Thus, TGF-β and WNT inhibitors jointly enhance GMT-induced direct cardiac reprogramming from cardiac fibroblasts in vitro and in vivo and provide a more robust platform for cardiac regeneration.
2016-10-25 | GSE81809 | GEO
Project description:BackgroundReprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells in situ represents a promising strategy for cardiac regeneration. A combination of 3 cardiac transcription factors, Gata4, Mef2c, and Tbx5 (GMT), can convert fibroblasts into induced cardiomyocyte-like cells, albeit with low efficiency in vitro.MethodsWe screened 5500 compounds in primary cardiac fibroblasts to identify the pathways that can be modulated to enhance cardiomyocyte reprogramming.ResultsWe found that a combination of the transforming growth factor-β inhibitor SB431542 and the WNT inhibitor XAV939 increased reprogramming efficiency 8-fold when added to GMT-overexpressing cardiac fibroblasts. The small molecules also enhanced the speed and quality of cell conversion; we observed beating cells as early as 1 week after reprogramming compared with 6 to 8 weeks with GMT alone. In vivo, mice exposed to GMT, SB431542, and XAV939 for 2 weeks after myocardial infarction showed significantly improved reprogramming and cardiac function compared with those exposed to only GMT. Human cardiac reprogramming was similarly enhanced on transforming growth factor-β and WNT inhibition and was achieved most efficiently with GMT plus myocardin.ConclusionsTransforming growth factor-β and WNT inhibitors jointly enhance GMT-induced direct cardiac reprogramming from cardiac fibroblasts in vitro and in vivo and provide a more robust platform for cardiac regeneration.
| S-EPMC5340593 | biostudies-literature
Project description:The direct conversion, or trans-differentiation, of non-cardiac cells into cardiomyocytes by forced expression of transcription factors and microRNAs provide promising ways of cardiac regeneration. However, genetic manipulations are still not desirable in real clinical applications. we report the generation of automatically beating cardiomyocyte-like cells from mouse fibroblasts with only chemical cocktails. These chemical-induced cardiomyocyte-like cells (CiCMs) express cardiomyocyte-specific markers, exhibit sarcomeric organization, and possess typical cardiac calcium flux and electrophysiological features. Microarray-bassed gene expression patterns of Mouse embryonic fibroblasts (MEFs), CiCMs, and cardiomyocytes(CMs) indicated a clear transition from dividing MEFs to differentiated cardiomyocyte-like state in CiCM samples. Mouse embryonic fibroblasts were treated with a small-molecule combination CRFVPT (10 μM CHIR99021 (C); 10 μM RepSox (R); 50 μM Forskolin (F); 0.5 mM VPA (V); 5 μM Parnate, (P); 1 μM TTNPB (T)) to induce transdifferentiation to chemical-induced cardiomyocyte-like cells. CiCMs beating clusters were picked at day 24 for analysis. MEFs were isolated from mouse embryos, and CMs were isolated from mouse hearts. Total RNA of MEFs, CiCMs and CMs were extracted and hybridization on Affymetrix microarrays.
2015-08-23 | E-GEOD-69924 | biostudies-arrayexpress
Project description:The direct conversion, or trans-differentiation, of non-cardiac cells into cardiomyocytes by forced expression of transcription factors and microRNAs provide promising ways of cardiac regeneration. However, genetic manipulations are still not desirable in real clinical applications. we report the generation of automatically beating cardiomyocyte-like cells from mouse fibroblasts with only chemical cocktails. These chemical-induced cardiomyocyte-like cells (CiCMs) express cardiomyocyte-specific markers, exhibit sarcomeric organization, and possess typical cardiac calcium flux and electrophysiological features. Microarray-bassed gene expression patterns of Mouse embryonic fibroblasts (MEFs), CiCMs, and cardiomyocytes(CMs) indicated a clear transition from dividing MEFs to differentiated cardiomyocyte-like state in CiCM samples.
2015-08-23 | GSE69924 | GEO
Project description:Pseudouridine-chemical probes-Nanopore direct RNA sequencing
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Project description:Direct in vivo cardiac reprogramming improves cardiac function and ventricular remodeling in chronic MI.
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Project description:Gata5 efficiently promotes cardiomyocyte fate from murine ESCs.By removing serum from the culture conditions, GATA4 and GATA6 are each also able to efficiently promote cardiogenesis in ESC derivatives, with some distinctions. Thus, GATA factors can function in ESC derivatives upstream of other cardiac transcription factors to direct specification of progenitors with cardiac potential. We used microarray to compared the global gene expression of Gata5-induced cardiac cells with other growth factor directed ESC-derived cardiac cells iGata5 ESCs were induced with doxycycline at day 4 and harvested at day16 for RNA extraction and hybridization on Affymetrix microarrays.
2013-02-02 | E-GEOD-43831 | biostudies-arrayexpress
Project description:Analysis of induced cardiomyocytes during direct cardiac reprogramming
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Project description:Heart failure (HF) is a leading cause of morbidity and mortality. As adult cardiomyocytes (CMs) have little regenerative capacity, after myocardial infarction (MI), resident cardiac fibroblasts (CFs) synthesize extracellular matrix to form scar tissues, resulting in myocardial remodeling and HF. Thus, both cardiac regeneration and fibrosis are therapeutic targets for chronic MI. We previously reported that fibroblasts were directly reprogrammed into induced CMs (iCMs) by overexpression of cardiogenic transcription factors in acute and chronic MI. Here we show that in vivo cardiac reprogramming improved cardiac function, and reversed cardiac remodeling in chronic MI using a novel transgenic mouse system. Transcriptome analysis revealed that in vivo cardiac reprogramming suppressed signs of fibrosis and inflammation. Thus, in vivo cardiac reprogramming may be a promising approach for chronic HF.
2024-07-01 | GSE240310 | GEO
Project description:Gata5 efficiently promotes cardiomyocyte fate from murine ESCs.By removing serum from the culture conditions, GATA4 and GATA6 are each also able to efficiently promote cardiogenesis in ESC derivatives, with some distinctions. Thus, GATA factors can function in ESC derivatives upstream of other cardiac transcription factors to direct specification of progenitors with cardiac potential. We used microarray to compared the global gene expression of Gata5-induced cardiac cells with other growth factor directed ESC-derived cardiac cells
2013-02-02 | GSE43831 | GEO