Document Detail

c-kit+ precursors support postinfarction myogenesis in the neonatal, but not adult, heart.
MedLine Citation:
PMID:  22847442     Owner:  NLM     Status:  MEDLINE    
We examined the myogenic response to infarction in neonatal and adult mice to determine the role of c-kit(+) cardiovascular precursor cells (CPC) that are known to be present in early heart development. Infarction of postnatal day 1-3 c-kit(BAC)-EGFP mouse hearts induced the localized expansion of (c-kit)EGFP(+) cells within the infarct, expression of the c-kit and Nkx2.5 mRNA, myogenesis, and partial regeneration of the infarction, with (c-kit)EGFP(+) cells adopting myogenic and vascular fates. Conversely, infarction of adult mice resulted in a modest induction of (c-kit)EGFP(+) cells within the infarct, which did not express Nkx2.5 or undergo myogenic differentiation, but adopted a vascular fate within the infarction, indicating a lack of authentic CPC. Explantation of infarcted neonatal and adult heart tissue to scid mice, and adoptive transfer of labeled bone marrow, confirmed the cardiac source of myogenic (neonate) and angiogenic (neonate and adult) cells. FACS-purified (c-kit)EGFP(+)/(αMHC)mCherry(-) (noncardiac) cells from microdissected infarcts within 6 h of infarction underwent cardiac differentiation, forming spontaneously beating myocytes in vitro; cre/LoxP fate mapping identified a noncardiac population of (c-kit)EGFP(+) myocytes within infarctions, indicating that the induction of undifferentiated precursors contributes to localized myogenesis. Thus, adult postinfarct myogenic failure is likely not due to a context-dependent restriction of precursor differentiation, and c-kit induction following injury of the adult heart does not define precursor status.
Sophy A Jesty; Michele A Steffey; Frank K Lee; Martin Breitbach; Michael Hesse; Shaun Reining; Jane C Lee; Robert M Doran; Alexander Yu Nikitin; Bernd K Fleischmann; Michael I Kotlikoff
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-30
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-15     Completed Date:  2012-10-29     Revised Date:  2014-10-21    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13380-5     Citation Subset:  IM    
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MeSH Terms
Aging / metabolism,  pathology*
Animals, Newborn
Cell Lineage
Endothelial Cells / metabolism,  pathology
Green Fluorescent Proteins / metabolism
Muscle Development*
Myocardial Infarction / metabolism,  pathology*
Proto-Oncogene Proteins c-kit / metabolism*
Stem Cells / cytology*,  metabolism
Grant Support
Reg. No./Substance:
0/enhanced green fluorescent protein; 147336-22-9/Green Fluorescent Proteins; EC Proteins c-kit
Comment In:
Stem Cell Reports. 2014 Jul 8;3(1):2   [PMID:  25068115 ]

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