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Series GSE68509 Query DataSets for GSE68509
Status Public on Oct 01, 2015
Title Akt1/Protein Kinase B Enhances Transcriptional Reprogramming of Fibroblasts to Functional Cardiomyocytes
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Conversion of fibroblasts to functional cardiomyocytes represents a potential approach for restoring cardiac function following myocardial injury, but the technique thus far has been slow and inefficient. To improve the efficiency of reprogramming fibroblasts to cardiac-like myocytes (iCMs) by cardiac transcription factors (Gata4, Hand2, Mef2c, and Tbx5=GHMT), we screened 192 protein kinases and discovered that Akt/protein kinase B dramatically accelerates and amplifies this process. Approximately 50% of reprogrammed fibroblasts displayed spontaneous beating after three weeks of induction by Akt plus GHMT. Furthermore, addition of Akt1 to GHMT evoked a more mature cardiac phenotype for iCMs, as seen by enhanced polynucleation, cellular hypertrophy, gene expression, and metabolic reprogramming. Igf1 and Pi3 kinase acted upstream of Akt, whereas mTORC1 and Foxo3a acted downstream of Akt to influence fibroblast-to-cardiomyocyte reprogramming. These findings provide new insights into the molecular basis of cardiac reprogramming and represent an important step toward further application of this technique.
Overall design We performed RNA-Seq using either isolated adult mouse ventricular cardiomyocytes (CMs) or MEFs treated for three weeks with empty vector, GHMT (iCMs cell sorted using αMHC-GFP before RNA-Seq), or AGHMT (iCMs cell sorted using αMHC-GFP before RNA-Seq).
Contributor(s) Zhou H, Dickson ME, Bassel-Duby R, Olson EN
Citation(s) 26354121
Submission date May 04, 2015
Last update date May 15, 2019
Contact name Min Soo Kim
Organization name University of Texas Southwestern
Department Department of Clinical Sciences
Lab Quantitative Biomedical Research Center
Street address 5323 Harry Hines Blvd.
City Dallas
State/province Texas
ZIP/Postal code 75390
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (12)
GSM1674060 GHMT_1
GSM1674061 GHMT_2
GSM1674062 GHMT_3
BioProject PRJNA282949
SRA SRP057984

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

Supplementary file Size Download File type/resource
GSE68509_DESeqNormalizedReadCounts.txt.gz 1.2 Mb (ftp)(http) TXT
GSE68509_RAW.tar 1.8 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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