Document Detail


A critical role for AID in the initiation of reprogramming to induced pluripotent stem cells.
MedLine Citation:
PMID:  23212122     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mechanistic insights into the reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) are limited, particularly for early acting molecular regulators. Here we use an acute loss of function approach to demonstrate that activation-induced deaminase (AID) activity is necessary for the initiation of reprogramming to iPSCs. While AID is well known for antibody diversification, it has also recently been shown to have a role in active DNA demethylation in reprogramming toward pluripotency and development. These findings suggested a potential role for AID in iPSC generation, yet, iPSC yield from AID-knockout mouse fibroblasts was similar to that of wild-type (WT) fibroblasts. We reasoned that an acute loss of AID function might reveal effects masked by compensatory mechanisms during development, as reported for other proteins. Accordingly, we induced an acute reduction (>50%) in AID levels using 4 different shRNAs and determined that reprogramming to iPSCs was significantly impaired by 79 ± 7%. The deaminase activity of AID was critical, as coexpression of WT but not a catalytic mutant AID rescued reprogramming. Notably, AID was required only during a 72-h time window at the onset of iPSC reprogramming. Our findings show a critical role for AID activity in the initiation of reprogramming to iPSCs.
Authors:
Nidhi Bhutani; Matthew N Decker; Jennifer J Brady; Rose T Bussat; David M Burns; Stephane Y Corbel; Helen M Blau
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-12-04
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  27     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-01     Completed Date:  2013-04-26     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1107-13     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Dedifferentiation*
Cell Line
Cytidine Deaminase / biosynthesis*,  genetics
Fibroblasts / cytology,  enzymology*
Humans
Induced Pluripotent Stem Cells / cytology,  enzymology*
Mice
Mice, Inbred BALB C
Mice, Knockout
Time Factors
Grant Support
ID/Acronym/Agency:
AG020961/AG/NIA NIH HHS; AG09521/AG/NIA NIH HHS; HL096113/HL/NHLBI NIH HHS; HL100397/HL/NHLBI NIH HHS; R01 AG009521/AG/NIA NIH HHS; R01 AG020961/AG/NIA NIH HHS; R01 AR063963/AR/NIAMS NIH HHS; R01 HL096113/HL/NHLBI NIH HHS; T32 CA009151/CA/NCI NIH HHS; T32CA09151/CA/NCI NIH HHS; U01 HL100397/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase
Comments/Corrections

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