Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart.
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.
Wu
Sean M
SM
Division of Hematology/Oncology, Children's Hospital, Boston, MA 02115, USA.
Fujiwara
Yuko
Y
Cibulsky
Susan M
SM
Clapham
David E
DE
Lien
Ching-Ling
CL
Schultheiss
Thomas M
TM
Orkin
Stuart H
SH
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
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