Document Detail

Sox2 Acts in a Dose-Dependent Fashion to Regulate Proliferation of Cortical Progenitors.
MedLine Citation:
PMID:  25482558     Owner:  NLM     Status:  Publisher    
Organ formation and maintenance depends on slowly self-renewing stem cells that supply an intermediate population of rapidly dividing progenitors, but how this proliferative hierarchy is regulated is unknown. By performing genome-wide single-cell and functional analyses in the cortex, we demonstrate that reduced Sox2 expression is a key regulatory signature of the transition between stem cells and rapidly dividing progenitors. In stem cells, Sox2 is expressed at high levels, which enables its repression of proproliferative genes, of which Cyclin D1 is the most potent target. Sox2 confers this function through binding to low-affinity motifs, which facilitate the recruitment of Gro/Tle corepressors in synergy with Tcf/Lef proteins. Upon differentiation, proneural factors reduce Sox2 expression, which derepresses Cyclin D1 and promotes proliferation. Our results show how concentration-dependent Sox2 occupancy of DNA motifs of varying affinities translates into recruitment of repressive complexes, which regulate the proliferative dynamics of neural stem and progenitor cells.
Daniel W Hagey; Jonas Muhr
Related Documents :
8218598 - The functional state of the beta cell modulates il-1 and tnf-induced cytotoxicity.
25486048 - Prion diseases and adult neurogenesis: how do prions counteract the brain's endogenous ...
25249758 - Cat amniotic membrane multipotent cells are nontumorigenic and are safe for use in cell...
12719268 - Analysis of cell kinetics using a cell division marker: mathematical modeling of experi...
17464188 - The present status of cell tracking methods in animal models using magnetic resonance i...
8355128 - Lymphocyte subpopulations in healthy newborn infants: comparison of cord blood values w...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-12-3
Journal Detail:
Title:  Cell reports     Volume:  -     ISSN:  2211-1247     ISO Abbreviation:  Cell Rep     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-8     Completed Date:  -     Revised Date:  2014-12-9    
Medline Journal Info:
Nlm Unique ID:  101573691     Medline TA:  Cell Rep     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Previous Document:  Loss of Abhd5 Promotes Colorectal Tumor Development and Progression by Inducing Aerobic Glycolysis a...
Next Document:  Regulatory T Cells Occupy an Isolated Niche in the Intestine that Is Antigen Independent.