Document Detail


Nuclear reprogramming in heterokaryons is rapid, extensive, and bidirectional.
MedLine Citation:
PMID:  19141533     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An understanding of nuclear reprogramming is fundamental to the use of cells in regenerative medicine. Due to technological obstacles, the time course and extent of reprogramming of cells following fusion has not been assessed to date. Here, we show that hundreds of genes are activated or repressed within hours of fusion of human keratinocytes and mouse muscle cells in heterokaryons, and extensive changes are observed within 4 days. This study was made possible by the development of a broadly applicable approach, species-specific transcriptome amplification (SSTA), which enables global resolution of transcripts derived from the nuclei of two species, even when the proportions of species-specific transcripts are highly skewed. Remarkably, either phenotype can be dominant; an excess of primary keratinocytes leads to activation of the keratinocyte program in muscle cells and the converse is true when muscle cells are in excess. We conclude that nuclear reprogramming in heterokaryons is rapid, extensive, bidirectional, and dictated by the balance of regulators contributed by the cell types.
Authors:
Adam Palermo; Regis Doyonnas; Nidhi Bhutani; Jason Pomerantz; Ozan Alkan; Helen M Blau
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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:  2009-01-13
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  23     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-01     Completed Date:  2009-05-26     Revised Date:  2013-03-18    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1431-40     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology and Stem Cell Institute, Stanford University School of Medicine, 269 Campus Dr., Stanford, CA 94305-5175, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation
Cell Fusion
Gene Expression Profiling / methods*
Humans
Hybrid Cells / metabolism,  physiology*
Keratinocytes / physiology
Mice
Nuclear Reprogramming*
Oligonucleotide Array Sequence Analysis
Grant Support
ID/Acronym/Agency:
AF051678/AF/ACF HHS; AG009521/AG/NIA NIH HHS; AG020961/AG/NIA NIH HHS; AG024987/AG/NIA NIH HHS; HD018179/HD/NICHD NIH HHS; R01 AG009521/AG/NIA NIH HHS; R01 AG009521-25/AG/NIA NIH HHS
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