Document Detail

Mammalian myotube dedifferentiation induced by newt regeneration extract.
MedLine Citation:
PMID:  11717431     Owner:  NLM     Status:  MEDLINE    
Newts are capable of regenerating several anatomical structures and organs, including their limbs. This remarkable regenerative capacity is thought to depend on cellular dedifferentiation. Terminally differentiated mammalian cells, by contrast, are normally incapable of reversing the differentiation process. Several factors could explain the absence of cellular dedifferentiation in mammals: (i) inadequate expression of genes that initiate dedifferentiation; (ii) insufficient intracellular signaling pathways; (iii) irreversible expression of differentiation factors; and (iv) structural characteristics that make dedifferentiation impossible. To investigate the causes underlying the lack of cellular plasticity in mammalian cells, we examined the effect of an extract derived from newt regenerating limbs on terminally differentiated mouse C2C12 myotubes. Approximately 18% of murine myotubes reentered the cell cycle when treated with regeneration extract, whereas 25% of newt myotubes exhibited cell cycle reentry. The muscle differentiation proteins MyoD, myogenin, and troponin T were reduced to undetectable levels in 15-30% of treated murine myotubes. We observed cellular cleavage in 11% of the treated murine myotubes and approximately 50% of these myotubes continued to cleave to produce proliferating mononucleated cells. These data indicate that mammalian myotubes can dedifferentiate when stimulated with the appropriate factors and suggest that one mechanism preventing dedifferentiation of mammalian cells is inadequate spatial or temporal expression of genes that initiate dedifferentiation.
C J McGann; S J Odelberg; M T Keating
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  98     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-21     Completed Date:  2002-01-08     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13699-704     Citation Subset:  IM    
Department of Internal Medicine, Division of Cardiology, University of Utah, Salt Lake City, UT 84112, USA.
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MeSH Terms
Cell Differentiation
Cell Extracts
Cell Line
Muscles / cytology*
MyoD Protein / metabolism
Myogenin / metabolism
Proteins / metabolism
Regeneration / physiology*
Salamandridae / metabolism*
Reg. No./Substance:
0/Cell Extracts; 0/MyoD Protein; 0/Myog protein, mouse; 0/Myogenin; 0/Proteins

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