title: Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart.
abstract: Despite recent advances in delineating the mechanisms involved in cardiogenesis, cellular lineage specification remains incompletely understood. To explore the relationship between developmental fate and potential, we isolated a cardiac-specific Nkx2.5(+) cell population from the developing mouse embryo. The majority of these cells differentiated into cardiomyocytes and conduction system cells. Some, surprisingly, adopted a smooth muscle fate. To address the clonal origin of these lineages, we isolated Nkx2.5(+) cells from in vitro differentiated murine embryonic stem cells and found approximately 28% of these cells expressed c-kit. These c-kit(+) cells possessed the capacity for long-term in vitro expansion and differentiation into both cardiomyocytes and smooth muscle cells from a single cell. We confirmed these findings by isolating c-kit(+)Nkx2.5(+) cells from mouse embryos and demonstrated their capacity for bipotential differentiation in vivo. Taken together, these results support the existence of a common precursor for cardiovascular lineages in the mammalian heart.
authors.affiliation: Division of Hematology/Oncology, Children's Hospital, Boston, MA 02115, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Wu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Susan M
authors.initials: SM
authors.lastname: Cibulsky
authors.forename: David E
authors.initials: DE
authors.lastname: Clapham
authors.forename: Ching-Ling
authors.initials: CL
authors.lastname: Lien
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Schultheiss
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D019009:Proto-Oncogene Proteins c-kit