github link
Accession IconGSE44401

Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 significantly enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming

Organism Icon Mus musculus
Sample Icon 12 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Submitter Supplied Information

Description
Transient over-expression of defined combinations of master regulator genes can effectively induce cellular reprogramming: the acquisition of an alternative predicted phenotype from a differentiated cell lineage. This can be of particular importance in cardiac regenerative medicine wherein the heart lacks the capacity to heal itself, but simultaneously contains a large pool of fibroblasts. In this study we determined the cardio-inducing capacity of ten transcription factors to actuate cellular reprogramming of mouse embryonic fibroblasts into cardiomyocyte-like cells. Over-expression of transcription factors MYOCD and SRF alone or in conjunction with Mesp1 and SMARCD3 significantly enhanced the basal but necessary cardio-inducing effect of the previously reported GATA4, TBX5, and MEF2C. In particular, combinations of five or seven transcription factors significantly enhanced the activation of cardiac reporter vectors, and induced an upregulation of cardiac-specific genes. Global gene expression analysis also demonstrated a significantly greater cardio-inducing effect when the transcription factors MYOCD and SRF were used. Detection of cross-striated cells was highly dependent on the cell culture conditions and was enhanced by the addition of valproic acid and JAK inhibitor. Although we detected Ca2+ transient oscillations in the reprogrammed cells, we did not detect significant changes in resting membrane potential or spontaneously contracting cells. This study further elucidates the cardio-inducing effect of the transcriptional networks involved in cardiac cellular reprogramming, contributing to the ongoing rational design of a robust protocol required for cardiac regenerative therapies.
PubMed ID
Total Samples
12
Submitter’s Institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Specimen part
Processing Information
Additional Metadata
No rows found
Loading...