Document Detail

The cellular prion protein identifies bipotential cardiomyogenic progenitors.
MedLine Citation:
PMID:  19910576     Owner:  NLM     Status:  MEDLINE    
RATIONALE: The paucity of specific surface markers for cardiomyocytes and their progenitors has impeded the development of embryonic or pluripotent stem cell-based transplantation therapy. Identification of relevant surface markers may also enhance our understanding of the mechanisms underlying differentiation. OBJECTIVE: Here, we show that cellular prion protein (PrP) serves as an effective surface marker for isolating nascent cardiomyocytes as well as cardiomyogenic progenitors. METHODS AND RESULTS: Embryonic stem (or embryo-derived) cells were analyzed using flow cytometry to detect surface expression of PrP and intracellular myosin heavy chain (Myhc) proteins. Sorted cells were then analyzed for their differentiation potential. CONCLUSIONS: PrP+ cells from beating embryoid bodies (EBs) frequently included nascent Myhc+ cardiomyocytes. Cultured PrP+ cells further differentiated, giving rise to cardiac troponin I+ definitive cardiomyocytes with either an atrial or a ventricular identity. These cells were electrophysiologically functional and able to survive in vivo after transplantation. Combining PrP with a second marker, platelet-derived growth factor receptor (PDGFR)alpha, enabled us to identify an earlier cardiomyogenic population from prebeating EBs, the PrP+PDGFRalpha+ (PRa) cells. The Myhc- PRa cells expressed cardiac transcription factors, such as Nkx2.5, T-box transcription factor 5, and Isl1 (islet LIM homeobox 1), although they were not completely committed. In mouse embryos, PRa cells in cardiac crescent at the 1 to 2 somite stage were Myhc+, whereas they were Myhc- at headfold stages. PRa cells clonally expanded in methlycellulose cultures. Furthermore, single Myhc- PRa cell-derived colonies contained both cardiac and smooth muscle cells. Thus, PrP demarcates a population of bipotential cardiomyogenic progenitor cells that can differentiate into cardiac or smooth muscle cells.
Kyoko Hidaka; Manabu Shirai; Jong-Kook Lee; Takanari Wakayama; Itsuo Kodama; Michael D Schneider; Takayuki Morisaki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-12
Journal Detail:
Title:  Circulation research     Volume:  106     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-08     Completed Date:  2010-01-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  111-9     Citation Subset:  IM    
Department of Bioscience, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
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MeSH Terms
Antigens, Differentiation / biosynthesis*,  genetics
Cell Differentiation / physiology*
Cells, Cultured
Embryonic Stem Cells / cytology,  metabolism*
Gene Expression Regulation, Developmental / physiology*
Homeodomain Proteins / biosynthesis,  genetics
Myocytes, Cardiac / cytology,  metabolism*
Myocytes, Smooth Muscle / cytology,  metabolism
Myosin Heavy Chains / biosynthesis,  genetics
Pluripotent Stem Cells / cytology,  metabolism*
Prions / biosynthesis*,  genetics
Receptor, Platelet-Derived Growth Factor alpha / biosynthesis,  genetics
Somites / cytology,  embryology
T-Box Domain Proteins / biosynthesis,  genetics
Transcription Factors / biosynthesis,  genetics
Troponin I / biosynthesis,  genetics
Grant Support
//British Heart Foundation
Reg. No./Substance:
0/Antigens, Differentiation; 0/Homeodomain Proteins; 0/Myosin Heavy Chains; 0/Nkx2-5 protein, mouse; 0/Prions; 0/T-Box Domain Proteins; 0/T-box transcription factor 5; 0/Transcription Factors; 0/Troponin I; 0/insulin gene enhancer binding protein Isl-1; EC, Platelet-Derived Growth Factor alpha
Comment In:
Circ Res. 2010 Jan 8;106(1):4-6   [PMID:  20056937 ]

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