NDLI: Role of the ATP- binding cassette transporter Abcg2 in the phenotype and function of cardiac side population cells

Content Provider	PubMed Central
Author	Pfister, Otmar Oikonomopoulos, Angelos Sereti, Konstantina-ioanna Sohn, Regina L. Cullen, Darragh Fine, Gabriel C. Mouquet, Frédéric Westerman, Karen Liao, Ronglih
Abstract	Recently, the side population (SP) phenotype has been introduced as a reliable marker to identify subpopulations of cells with stem/progenitor cell properties in various tissues. We and others have identified SP cells from post-mitotic tissues, including adult myocardium, in which they have been suggested to contribute to cellular regeneration following injury. SP cells are identified and characterized by a unique efflux of Hoechst 33342 dye. Abcg2 belongs to the ATP-binding cassette (ABC) transporter superfamily and constitutes the molecular basis for the dye efflux, hence the SP phenotype, in hematopoietic stem cells. While Abcg2 is also expressed in cardiac SP (cSP) cells, its role in regulating the SP phenotype and function of cSP cells is unknown. Herein, we demonstrate that regulation of the SP phenotype in cSP cells occurs in a dynamic, age-dependent fashion, with Abcg2 as the molecular determinant of the cSP phenotype in the neonatal heart and another ABC transporter, Mdr1, as the main contributor to the SP phenotype in the adult heart. Using loss- and gain-of-function experiments we find that Abcg2 tightly regulates cell fate and function. Adult cSP cells isolated from mice with genetic ablation of Abcg2, exhibit blunted proliferation capacity and augmented cell death. Conversely, overexpression of Abcg2 is sufficient to enhance cell proliferation, though with a limitation of cardiomyogenic differentiation. In summary, for the first time, we reveal a functional role for Abcg2 in modulating the proliferation, differentiation, and survival of adult cSP cells that goes beyond its distinct role in Hoechst dye efflux.
Related Links	http://dx.doi.org/10.1161/circresaha.108.174615
Ending Page	835
Page Count	11
Starting Page	825
File Format	PDF
ISSN	00097330
e-ISSN	15244571
Journal	Circulation research
Issue Number	8
Volume Number	103
Language	English
Publisher Date	2008-10-10
Access Restriction	Open
Subject Keyword	Physiology Cardiology and Cardiovascular Medicine Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology Cardiology and Cardiovascular Medicine

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