Document Detail


Sodium butyrate promotes generation of human induced pluripotent stem cells through induction of the miR302/367 cluster.
MedLine Citation:
PMID:  23534850     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Small molecules (SM) can greatly enhance the efficiency of induced pluripotent stem (iPS) cell generation, but the mechanisms by which they act have not been fully explored. We show here that an SM cocktail (NaB, PD03259, and SB431542) significantly promotes iPS cell generation from human fibroblasts, and NaB is more potent than the other two common histone deacetylase inhibitors (valproic acid and Trichostatin A) in promoting cellular reprogramming. Our data indicate that the SM cocktail substantially upregulates the miR302/367 cluster expression by increasing the stability and transcriptional level of this microRNA (miRNA) cluster in a manner dependent on the four defined transcription factors (TFs). Among the four TFs, Oct4 in particular appears to be required for the induction of the miR302/367 cluster by the SM cocktail. We also found that NaB alone can enhance the TFs-dependent upregulation of the miR302/367 cluster. Using a promoter reporter assay, we show that the SM cocktail remarkably enhanced the transcriptional activity of the four TFs in the miR302/367 promoter. Notably, attenuation of miRNA302/367 using a miRZip impairs the ability of the SM cocktail in promoting reprogramming. Collectively, these findings suggest that the SM cocktail promotes reprogramming at least partly through the induction of the miR302/367 cluster expression. Further insights into this process may pave the way for the generation of iPS cells using only SM cocktails.
Authors:
Zhonghui Zhang; Wen-Shu Wu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-04-27
Journal Detail:
Title:  Stem cells and development     Volume:  22     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-08-01     Completed Date:  2014-02-19     Revised Date:  2014-08-17    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2268-77     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzamides / pharmacology
Butyric Acid / pharmacology*
Cell Differentiation / drug effects
Dioxoles / pharmacology
Diphenylamine / analogs & derivatives,  pharmacology
Fibroblasts / cytology,  drug effects*,  metabolism
Gene Expression Profiling
Gene Expression Regulation
Humans
Induced Pluripotent Stem Cells / cytology,  drug effects*,  metabolism
MicroRNAs / genetics*,  metabolism
Nuclear Reprogramming / drug effects*
Octamer Transcription Factor-3 / genetics,  metabolism
Primary Cell Culture
Promoter Regions, Genetic
RNA Stability
Signal Transduction
Transcription Factors / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
R21 5R21HD061777/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; 0/Benzamides; 0/Dioxoles; 0/MIRN302 microRNA, human; 0/MIRN367 microRNA, human; 0/MicroRNAs; 0/Octamer Transcription Factor-3; 0/PD 0325901; 0/POU5F1 protein, human; 0/Transcription Factors; 107-92-6/Butyric Acid; 9N3CBB0BIQ/Diphenylamine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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