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Series GSE44401 Query DataSets for GSE44401
Status Public on Mar 31, 2013
Title Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 significantly enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
 
Overall design Mouse embryonic fibroblasts were transduced lentiviruses allowing the inducible overexpression of three unique sets of transcription factors and negative control. A total of four experimental groups which included three biological replicates in each.
 
Contributor(s) Christoforou N, Chellappan M, Adler AF, Kirkton RD, Wu T, Addis RC, Bursac N, Leong KW
Citation(s) 23704920
Submission date Feb 19, 2013
Last update date May 04, 2018
Contact name Nicolas Christoforou
E-mail(s) nc28@duke.edu
Organization name Duke University
Department Biomedical Engineering
Lab Dr. Kam Leong
Street address 136 Hudson Hall
City Durham
State/province North Carolina
ZIP/Postal code 27708
Country USA
 
Platforms (1)
GPL8321 [Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array
Samples (12)
GSM1084553 MEF_Negative Control 1
GSM1084554 MEF_Negative Control 2
GSM1084555 MEF_Negative Control 3
Relations
BioProject PRJNA189770

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Supplementary file Size Download File type/resource
GSE44401_RAW.tar 23.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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