Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart
Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart
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DOI：
10.1016/j.cell.2006.10.028
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发表时间：
2006-12-15
期刊：
影响因子：
64.5
通讯作者：
Orkin, Stuart H.
中科院分区：
文献类型：
--
作者：
Wu, Sean M.;Fujiwara, Yuko;Orkin, Stuart H.
尽管最近在描述心脏发生机制方面取得了进展，但细胞谱系规范仍不完全清楚。为了探索发育命运和潜力之间的关系，我们从发育中的小鼠胚胎中分离出心脏特异性的 Nkx2.5(+) 细胞群。这些细胞大多数分化为心肌细胞和传导系统细胞。令人惊讶的是，有些人接受了平滑肌的命运。为了解决这些谱系的克隆起源，我们从体外分化的小鼠胚胎干细胞中分离出 Nkx2.5+ 细胞，并发现这些细胞中有 28% 表达 c-kit。这些c-kit(+)细胞具有长期体外扩增和从单细胞分化为心肌细胞和平滑肌细胞的能力。我们通过从小鼠胚胎中分离c-kit(+)Nkx2.5(+)细胞证实了这些发现，并证明了它们在体内双潜能分化的能力。总而言之，这些结果支持哺乳动物心脏中心血管谱系的共同前体的存在。
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 similar to 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.