Document Detail


A late transition in somatic cell reprogramming requires regulators distinct from the pluripotency network.
MedLine Citation:
PMID:  23217423     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Reprogramming of somatic cells to a pluripotent state via expression of Oct4, Klf4, Myc, and Sox2 is a multistep process involving phased changes in gene expression. Here, we focus on the later stages of reprogramming, termed maturation and stabilization. We show that the stabilization phase and the acquisition of pluripotency are dependent on the removal of transgene expression late in the maturation phase. Clonal analysis of cells undergoing reprogramming revealed subsets of stabilization-competent (SC) and stabilization-incompetent (SI) cells. SC clones acquire a competency gene-expression signature late in the maturation phase. Functional analysis of SC signature genes identified enhancers of the transition to the stabilization phase and a distinct subset of genes required for the maintenance of pluripotency. Thus, the acquisition and maintenance of pluripotency are regulated by distinct molecular networks, and a specific regulatory program not previously implicated in reprogramming is required for the transition to transgene independence.
Authors:
Azadeh Golipour; Laurent David; Yu Liu; Gowtham Jayakumaran; Calley L Hirsch; Dan Trcka; Jeffrey L Wrana
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell stem cell     Volume:  11     ISSN:  1875-9777     ISO Abbreviation:  Cell Stem Cell     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101311472     Medline TA:  Cell Stem Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  769-82     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
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