title: Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification.
abstract: Cardiogenesis requires the generation of endothelial, cardiac, and smooth muscle cells, thought to arise from distinct embryonic precursors. We use genetic fate-mapping studies to document that isl1(+) precursors from the second heart field can generate each of these diverse cardiovascular cell types in vivo. Utilizing embryonic stem (ES) cells, we clonally amplified a cellular hierarchy of isl1(+) cardiovascular progenitors, which resemble the developmental precursors in the embryonic heart. The transcriptional signature of isl1(+)/Nkx2.5(+)/flk1(+) defines a multipotent cardiovascular progenitor, which can give rise to cells of all three lineages. These studies document a developmental paradigm for cardiogenesis, where muscle and endothelial lineage diversification arises from a single cell-level decision of a multipotent isl1(+) cardiovascular progenitor cell (MICP). The discovery of ES cell-derived MICPs suggests a strategy for cardiovascular tissue regeneration via their isolation, renewal, and directed differentiation into specific mature cardiac, pacemaker, smooth muscle, and endothelial cell types.
authors.affiliation: Massachusetts General Hospital - Cardiovascular Research Center, Charles River Plaza/CPZN 3208, 185 Cambridge Street, Boston, MA 02114, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Moretti
authors.forename: Leslie
authors.initials: L
authors.lastname: Caron
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakano
authors.forename: Jason T
authors.initials: JT
authors.lastname: Lam
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bernshausen
authors.forename: Yinhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Yibing
authors.initials: Y
authors.lastname: Qyang
authors.forename: Lei
authors.initials: L
authors.lastname: Bu
authors.forename: Mika
authors.initials: M
authors.lastname: Sasaki
authors.forename: Silvia
authors.initials: S
authors.lastname: Martin-Puig
authors.forename: Yunfu
authors.initials: Y
authors.lastname: Sun
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Laugwitz
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chien
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D002999:Clone Cells; D053595:Embryonic Stem Cells / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology*; D006321:Heart / Q000196:embryology; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D039902:Multipotent Stem Cells / Q000502:physiology*; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D014157:Transcription Factors
chemical_list: D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1