Université Libre de Bruxelles, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, B1070 Bruxelles, Belgium.
J Cell Biol. 2011 Mar 7;192(5):751-65. doi: 10.1083/jcb.201007063.
During embryonic development and embryonic stem cell (ESC) differentiation, the different cell lineages of the mature heart arise from two types of multipotent cardiovascular progenitors (MCPs), the first and second heart fields. A key question is whether these two MCP populations arise from differentiation of a common progenitor. In this paper, we engineered Mesp1-green fluorescent protein (GFP) ESCs to isolate early MCPs during ESC differentiation. Mesp1-GFP cells are strongly enriched for MCPs, presenting the ability to differentiate into multiple cardiovascular lineages from both heart fields in vitro and in vivo. Transcriptional profiling of Mesp1-GFP cells uncovered cell surface markers expressed by MCPs allowing their prospective isolation. Mesp1 is required for MCP specification and the expression of key cardiovascular transcription factors. Isl1 is expressed in a subset of early Mesp1-expressing cells independently of Mesp1 and acts together with Mesp1 to promote cardiovascular differentiation. Our study identifies the early MCPs residing at the top of the cellular hierarchy of cardiovascular lineages during ESC differentiation.
在胚胎发育和胚胎干细胞（ESC）分化过程中，成熟心脏的不同细胞谱系来自两种多能心血管祖细胞（MCP），即第一和第二心脏场。一个关键问题是这两种 MCP 群体是否来自共同祖细胞的分化。在本文中，我们设计了 Mesp1-绿色荧光蛋白（GFP）ESC 以在 ESC 分化过程中分离早期 MCP。Mesp1-GFP 细胞强烈富集 MCP，具有体外和体内从两个心脏场分化为多种心血管谱系的能力。对 Mesp1-GFP 细胞的转录谱分析揭示了 MCP 表达的细胞表面标记物，允许其进行预期的分离。Mesp1 对于 MCP 规范和关键心血管转录因子的表达是必需的。Isl1 在独立于 Mesp1 的早期 Mesp1 表达细胞的亚群中表达，并与 Mesp1 一起共同促进心血管分化。我们的研究确定了在 ESC 分化过程中位于心血管谱系细胞层次结构顶端的早期 MCP。
