Document Detail


Learning the molecular mechanisms of the reprogramming factors: let's start from microRNAs.
MedLine Citation:
PMID:  23037570     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Induced reprogramming of somatic cells has had a great impact on stem cell research, and the reprogramming technologies have evolved from four transgenic factors (Oct4, Sox2, Klf4, and c-Myc; OSKM) to just a few microRNAs (mainly miR-290/302 seed family). Despite these advances, the molecular events occurring during various stages of reprogramming remain largely unknown. Here, we concisely review current knowledge of miRNA regulation from the initiation phase of OSKM-induced reprogramming, through the transitional stage, to final maturation. At the start of reprogramming, the microRNAs miR-21, miR-29a, let-7a, and miR-34 act as guards to secure the somatic identity and genomic integrity of the cell of origin. As reprogramming proceeds, miR-155, miR-10b, miR-205, and miR-429 modulate the epithelial-mesenchymal/mesenchymal-epithelial transition (EMT/MET), which is a critical step towards transformed pluripotent status. Finally, the pluripotency regulatory network is secured in the iPSCs and fine-tuned by a group of miRNAs belonging to the miR-290/302 seed family. Among the four reprogramming factors, c-Myc plays the dominant role in regulating the miRNAs under reprogramming-specific conditions. Accumulating evidence suggests that the reprogramming efficiency can be improved by either blocking barrier miRNAs or introducing helper miRNAs. Intriguingly, induced pluripotency can be obtained by introducing a single miR-302 cluster, although the supportive molecular mechanism is still lacking. In the near future, we may be able to realize the broad potential of miRNAs in the stem cell field, such as altering cell identities with high efficiency through the transient introduction of tissue-specific miRNAs.
Authors:
Chao-Shun Yang; Tariq M Rana
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2012-10-05
Journal Detail:
Title:  Molecular bioSystems     Volume:  9     ISSN:  1742-2051     ISO Abbreviation:  Mol Biosyst     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-11-28     Completed Date:  2013-07-24     Revised Date:  2014-02-26    
Medline Journal Info:
Nlm Unique ID:  101251620     Medline TA:  Mol Biosyst     Country:  England    
Other Details:
Languages:  eng     Pagination:  10-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
DNA-Binding Proteins / genetics*,  metabolism
Humans
MicroRNAs / genetics*,  metabolism
Nuclear Reprogramming / physiology*
Grant Support
ID/Acronym/Agency:
P01 MH100942/MH/NIMH NIH HHS; R01 AI041404/AI/NIAID NIH HHS; R01 AI043198/AI/NIAID NIH HHS; R01 DA030199/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/MicroRNAs
Comments/Corrections

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