Document Detail


Progenitor cells identified by PDGFR-alpha expression in the developing and diseased human heart.
MedLine Citation:
PMID:  23391309     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Platelet-derived growth factors (PDGFs) and their tyrosine kinase receptors play instrumental roles in embryonic organogenesis and diseases of adult organs. In particular, platelet-derived growth factor receptor-alpha (PDGFRα) is expressed by multipotent cardiovascular progenitors in mouse and human embryonic stem cell systems. Although cardiac PDGFRα expression has been studied in multiple species, little is known about its expression in the human heart. Using immunofluorescence, we analyzed PDGFRα expression in both human fetal and diseased adult hearts, finding strong expression in the interstitial cells of the epicardium, myocardium, and endocardium, as well as the coronary smooth muscle. Only rare endothelial cells and cardiomyocytes expressed PDGFRα. This pattern was consistent for both the fetal and adult diseased hearts, although more PDGFRα+ cardiomyocytes were noted in the latter. In vitro differentiation assays were then performed on the PDGFRα+ cell fraction isolated from the cardiomyocyte-depleted human fetal hearts. Protocols previously reported to direct differentiation to a cardiomyocyte (5-azacytidine), smooth muscle (PDGF-BB), or endothelial cell fates (vascular endothelial growth factor [VEGF]) were used. Although no significant cardiomyocyte differentiation was observed, PDGFRα+ cells generated significant numbers of smooth muscle cells (smooth muscle-α-actin+ and smooth muscle myosin+) and endothelial cells (CD31+). These data suggest that a subfraction of the cardiac PDGFRα+ populations are progenitors contributing predominantly to the vascular and mesenchymal compartments of the human heart. It may be possible to control the fate of these progenitors to promote vascularization or limit fibrosis in the injured heart.
Authors:
James J H Chong; Hans Reinecke; Mineo Iwata; Beverly Torok-Storb; April Stempien-Otero; Charles E Murry
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-03-26
Journal Detail:
Title:  Stem cells and development     Volume:  22     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-17     Completed Date:  2014-02-13     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1932-43     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Azacitidine / pharmacology
Cell Differentiation / drug effects
Gene Expression Regulation, Developmental / drug effects
Heart Injuries / metabolism,  therapy
Humans
Lymphokines / biosynthesis*,  metabolism
Mice
Muscle, Smooth, Vascular / cytology,  drug effects,  growth & development
Myocardium / metabolism*,  pathology
Myocytes, Cardiac / cytology
Platelet-Derived Growth Factor / biosynthesis*,  metabolism
Receptor, Platelet-Derived Growth Factor alpha / biosynthesis*
Stem Cells / cytology,  drug effects,  metabolism*
Grant Support
ID/Acronym/Agency:
HL094384/HL/NHLBI NIH HHS; HL099993/HL/NHLBI NIH HHS; P01 GM081719/GM/NIGMS NIH HHS; P01 HL094374/HL/NHLBI NIH HHS; P01 HL094374/HL/NHLBI NIH HHS; R01 HL084642/HL/NHLBI NIH HHS; R01 HL084642/HL/NHLBI NIH HHS; R01 HL64387/HL/NHLBI NIH HHS; R24HD000836/HD/NICHD NIH HHS; U01 HL099993/HL/NHLBI NIH HHS; U01 HL100405/HL/NHLBI NIH HHS; U01 HL100405/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Lymphokines; 0/PDGFD protein, human; 0/Platelet-Derived Growth Factor; EC 2.7.10.1/Receptor, Platelet-Derived Growth Factor alpha; M801H13NRU/Azacitidine
Comments/Corrections

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