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Series GSE43588 Query DataSets for GSE43588
Status Public on Jan 18, 2013
Title Reprogramming of human fibroblasts toward a cardiac fate
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Reprogramming of mouse fibroblasts toward a myocardial cell fate by forced expression of cardiac transcription factors or microRNAs has recently been demonstrated. The potential clinical applicability of these findings is based on the minimal regenerative potential of the adult human heart and the limited availability of human heart tissue. An initial, but mandatory step toward clinical application of this approach is to establish conditions for conversion of adult human fibroblasts to a cardiac phenotype. Toward this goal, we sought to determine the optimal combination of factors necessary and sufficient for direct myocardial reprogramming of human fibroblasts. Here we show that four human cardiac transcription factors, including Gata4, Hand2, Tbx5, and myocardin, and two microRNAs, miR-1 and miR-133, activated cardiac marker expression in neonatal and adult human fibroblasts. After maintenance in culture for 4-11 weeks, human fibroblasts reprogrammed with these proteins and microRNAs displayed sarcomere-like structures and calcium transients, and a small subset of such cells exhibited spontaneous contractility. These phenotypic changes were accompanied by expression of a broad range of cardiac genes and suppression of non-myocyte genes. These findings indicate that human fibroblasts can be reprogrammed to cardiac-like myocytes by forced expression of cardiac transcription factors with muscle-specific microRNAs and represent a step toward possible therapeutic application of this reprogramming approach.
 
Overall design Human foreskin fibroblasts were transduced with 5 transcription factors and total RNA was obtained 4 weeks later. total RNA was also obtained from human foreskin fibroblasts as a negative control and adult human heart tissue as a positive control. The expression level of genes in each sample was compared.
 
Contributor(s) Nam Y, Olson EN
Citation(s) 23487791
Submission date Jan 17, 2013
Last update date Jul 26, 2018
Contact name young-jae Nam
E-mail(s) young-jae.nam@utsouthwestern.edu
Organization name UT Southwestern Medical Center
Street address 5323 Harry Hines Blvd
City Dallas
ZIP/Postal code 75235
Country USA
 
Platforms (1)
GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version]
Samples (3)
GSM1065980 5F
GSM1065981 Adult heart
GSM1065982 HFF
Relations
BioProject PRJNA186780

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE43588_RAW.tar 12.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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