| c-kit+ precursors support postinfarction myogenesis in the neonatal, but not adult, heart. | |
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MedLine Citation:
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PMID: 22847442 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-07-30 |
Journal Detail:
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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:
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Created Date: 2012-08-15 Completed Date: 2012-10-29 Revised Date: 2013-04-12 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 13380-5 Citation Subset: IM |
Affiliation:
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Department of Biomedical Science, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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metabolism,
pathology* Animals Animals, Newborn Cell Lineage Endothelial Cells / metabolism, pathology Green Fluorescent Proteins / metabolism Mice Muscle Development* Myocardial Infarction / metabolism, pathology* Proto-Oncogene Proteins c-kit / metabolism* Regeneration Stem Cells / cytology*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK065992/DK/NIDDK NIH HHS; DK072277/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/enhanced green fluorescent protein; 147336-22-9/Green Fluorescent Proteins; EC 2.7.10.1/Proto-Oncogene Proteins c-kit |
| Comments/Corrections | |
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