title: Integrin Based Isolation Enables Purification of Murine Lineage Committed Cardiomyocytes.
abstract: In contrast to mature cardiomyocytes which have limited regenerative capacity, pluripotent stem cells represent a promising source for the generation of new cardiomyocytes. The tendency of pluripotent stem cells to form teratomas and the heterogeneity from various differentiation stages and cardiomyocyte cell sub-types, however, are major obstacles to overcome before this type of therapy could be applied in a clinical setting. Thus, the identification of extracellular markers for specific cardiomyocyte progenitors and mature subpopulations is of particular importance. The delineation of cardiomyocyte surface marker patterns not only serves as a means to derive homogeneous cell populations by FACS, but is also an essential tool to understand cardiac development. By using single-cell expression profiling in early mouse embryonic hearts, we found that a combination of integrin alpha-1, alpha-5, alpha-6 and N-cadherin enables isolation of lineage committed murine cardiomyocytes. Additionally, we were able to separate trabecular cardiomyocytes from solid ventricular myocardium and atrial murine cells. These cells exhibit expected subtype specific phenotype confirmed by electrophysiological analysis. We show that integrin expression can be used for the isolation of living, functional and lineage-specific murine cardiomyocytes.
authors: Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
authors: Laura
authors: L
authors: Tarnawski
authors: Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
authors: Xiaojie
authors: X
authors: Xian
authors: Institute of Physiology I, Life and Brain Center, Department of Cardiac Surgery, University of Bonn, Bonn, Germany; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Gustavo
authors: G
authors: Monnerat
authors: Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, England.
authors: Iain C
authors: IC
authors: Macaulay
authors: Institute of Physiology I, Life and Brain Center, Department of Cardiac Surgery, University of Bonn, Bonn, Germany.
authors: Daniela
authors: D
authors: Malan
authors: Spectrum Health Fredrik Meijer Heart and Vascular Institute, Grand Rapids, Michigan, United States of America.
authors: Andrew
authors: A
authors: Borgman
authors: Institute for Stem Cell Biology and Regenerative Medicine, Stanford, California, United States of America; Stanford Cardiovascular Institute, Stanford, California, United States of America; Dept of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California, United States of America.
authors: Sean M
authors: SM
authors: Wu
authors: Institute of Physiology I, Life and Brain Center, Department of Cardiac Surgery, University of Bonn, Bonn, Germany; Pharma Center Bonn, University of Bonn, Bonn, Germany.
authors: Bernd K
authors: BK
authors: Fleischmann
authors: Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden; Van Andel Research Institute, Grand Rapids, Michigan, United States of America; Spectrum Health Fredrik Meijer Heart and Vascular Institute, Grand Rapids, Michigan, United States of America.
authors: Stefan
authors: S
authors: Jovinge
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D020869:Gene Expression Profiling / Q000379:methods; D016023:Integrins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015820:Cadherins; D016023:Integrins