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Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions, in which conversion of partially reprogrammed cells into fully reprogrammed functional iCMs has been a major hurdle. Here, we report that a combination of fibroblast growth factor (FGF) 2, FGF10, and vascular endothelial growth factor (VEGF), termed FFV, promoted cardiac reprogramming under defined serum-free conditions, increasing spontaneously beating iCMs by 100-fold compared with those under conventional serum-based conditions. Mechanistically, FFV activated multiple cardiac transcriptional regulators and converted partially reprogrammed cells into functional iCMs through the p38 mitogen-activated protein kinase and phosphoinositol 3-kinase/AKT pathways. Moreover, FFV enabled cardiac reprogramming with only Mef2c and Tbx5 through the induction of cardiac reprogramming factors, including Gata4. Thus, defined culture conditions promoted the quality of cardiac reprogramming, and this finding provides new insight into the mechanism of cardiac reprogramming.
Pubmed ID: 26626177 RIS Download
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Software to graphically browse results of clustering and other analyses from Cluster.
View all literature mentionsWeb-based tool for the ontological analysis of large lists of genes. It can be used to determine biological annotations or combinations of annotations that are significantly associated to a list of genes under study with respect to a reference list. As well as single annotations, this tool allows users to simultaneously evaluate annotations from different sources, for example Biological Process and Cellular Component categories of Gene Ontology.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsSoftware application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
View all literature mentionsSoftware R package. Methods for Cluster analysis. Performs variety of types of cluster analysis and other types of processing on large microarray datasets.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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