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Series GSE27329 Query DataSets for GSE27329
Status Public on Nov 30, 2012
Title Genome-Wide Analysis of Gene Program Activation by Defined Cardiac Transcription Factor Tbx5, Gata4 and Myocardin
Organism Mus musculus
Experiment type Expression profiling by array
Summary Background: Cardiac transcription factors are master regulators during heart development. Recently, some were shown to transdifferentiate noncardiac mesoderm cells and cardiac fibroblasts into cardiomyocytes. However, the individual roles of each transcription factors in activating cardiac gene program have not been elucidated. We examined cardiac-specific and genome-wide gene expression in fibroblasts induced with cardiac transcription factors Nkx2.5 (N), Tbx5 (T), Gata4 (G), Myocardin (M) alone or different combinations.

Methodology/Principal Findings: We applied different combinations of human Nkx2.5 (N), Tbx5 (T), Gata4 (G) and Myocardin (M) lentiviruses into 10T1/2 fibroblasts. Immunostaining and quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that N, T, G or M alone did not induce expression of cardiac marker genes α-myosin heavy chain (αMHC) and cardiac troponin T (cTnT). Only T+M and T+G+M combinations induced αMHC and cTnT expression. Microarray-based gene ontology analysis revealed that T alone inhibited most genes involved in cardiac-related processes and activated genes involved in Wnt receptor signaling pathway and in aberrant processes. M alone inhibited genes involved in Wnt receptor signaling pathway and activated genes involved in cardiac-related processes and in aberrant processes. G alone inhibited genes involved in ectoderm development. T+G+M combination was the most effective activator of genes associated with cardiac-related processes including muscle cell differentiation, sarcomere, striated muscle contraction, regulation of heart contraction, and glucose metabolism and fatty acid oxidation (two significant forms of cardiomyocyte energy metabolism). And unlike T, M, G alone or T+M, T+G+M did not activate genes associated with aberrant processes.

Conclusions: Tbx5, Gata4 and Myocardin play different roles in activating cardiac gene program and in avoiding aberrant gene program activation. The combination of T+G+M activated cardiac gene program and avoided aberrant gene program activation.
 
Overall design Two weeks after doxycline induction, total RNA was isolated from 10T1/2-tTA cells infected with different combinations of Tbx5, Gata4, and Myocardin lentiviruses. Biological triplicated.
 
Contributor(s) Zhou L, Liu Y, Dixon R, Lu L
Citation(s) 23144723
Submission date Feb 15, 2011
Last update date Feb 11, 2019
Contact name Lei Zhou
E-mail(s) lzhou@heart.thi.tmc.edu
Organization name Texas Heart Institute
Street address 6700 Bertner Avenue
City Houston
ZIP/Postal code 77030
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (24)
GSM675173 LacZ-1
GSM675199 LacZ-2
GSM675201 LacZ-3
Relations
BioProject PRJNA137309

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE27329_RAW.tar 87.5 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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