Document Detail


Tbx6 is a determinant of cardiac and neural cell fate decisions in multipotent P19CL6 cells.
MedLine Citation:
PMID:  22721678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multipotent P19CL6 cells differentiate into cardiac myocytes or neural lineages when stimulated with dimethyl sulfoxide (DMSO) or retinoic acid (RA), respectively. Expression of the transcription factor Tbx6 was found to increase during cardiac myocyte differentiation and to decrease during neural differentiation. Overexpression of Tbx6 was not sufficient to drive P19CL6 cells to a cardiac myocyte fate or to accelerate DMSO-induced differentiation. In contrast, knockdown of Tbx6 dramatically inhibited DMSO-induced differentiation of P19CL6 cells to cardiac myocytes, as evidenced by the loss of striated muscle-specific markers and spontaneous beating. Tbx6 knockdown was also accompanied by almost complete loss of Nkx2.5, a transcription factor involved in the specification of the cardiac myocyte lineage, indicating that Nkx2.5 is downstream of Tbx6. In distinction to its positive role in cardiac myocyte differentiation, Tbx6 knockdown augmented RA-induced differentiation of P19CL6 cells to both neurons and glia, and accelerated the rate of neurite formation. Conversely, Tbx6 overexpression attenuated differentiation to neural lineages. Thus, in the P19CL6 model, Tbx6 is required for cardiac myocyte differentiation and represses neural differentiation. We propose a model in which Tbx6 is a part of a molecular switch that modulates divergent differentiation programs within a single progenitor cell.
Authors:
Svetlana Gavrilov; Thomas G Nührenberg; Anthony W Ashton; Chang-Fu Peng; Jennifer C Moore; Klitos Konstantinidis; Christine L Mummery; Richard N Kitsis
Related Documents :
19306108 - Arylsulfatase b regulates colonic epithelial cell migration by effects on mmp9 expressi...
3536318 - Investigation of sloughed corneal epithelial cells collected by non-invasive irrigation...
12203728 - Transition between proliferation and differentiation for lens epithelial cells is regul...
16453018 - Mucus in chronic airway diseases: sorting out the sticky details.
7372068 - Effect of nicotine on the morphology of the rat gastric mucosa.
816748 - Effects of high-let particles (40a) on the brain of drosophila melanogaster.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-19
Journal Detail:
Title:  Differentiation; research in biological diversity     Volume:  84     ISSN:  1432-0436     ISO Abbreviation:  Differentiation     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-07-30     Completed Date:  2012-11-13     Revised Date:  2013-12-05    
Medline Journal Info:
Nlm Unique ID:  0401650     Medline TA:  Differentiation     Country:  England    
Other Details:
Languages:  eng     Pagination:  176-84     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation*
Cell Line, Tumor
Cell Lineage
Dimethyl Sulfoxide / pharmacology
Homeodomain Proteins / metabolism
Mice
Multipotent Stem Cells / cytology*,  drug effects
Myocytes, Cardiac / cytology*
Neurons / cytology*
RNA, Small Interfering
Transcription Factors / antagonists & inhibitors,  metabolism*
Tretinoin / pharmacology
Grant Support
ID/Acronym/Agency:
R01 HL060665/HL/NHLBI NIH HHS; R01 HL061550/HL/NHLBI NIH HHS; R01 HL080607/HL/NHLBI NIH HHS; R01 HL60665/HL/NHLBI NIH HHS; R01 HL61550/HL/NHLBI NIH HHS; R01 HL80607/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Homeodomain Proteins; 0/Nkx2-5 protein, mouse; 0/RNA, Small Interfering; 0/Tbx6 protein, mouse; 0/Transcription Factors; 5688UTC01R/Tretinoin; YOW8V9698H/Dimethyl Sulfoxide
Comments/Corrections

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


Previous Document:  Understanding help-seeking decisions in people with heart failure: A qualitative systematic review.
Next Document:  Assessment of a formulation designed to be crush-resistant in prescription opioid abusers.