Defining the earliest step of cardiovascular progenitor specification during embryonic stem cell differentiation.

Defining the earliest step of cardiovascular progenitor specification during embryonic stem cell differentiation.
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DOI:
10.1083/jcb.201007063
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发表时间:
2011-03-07
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Blanpain C
Blanpain C
中科院分区:
其他
文献类型:
--
作者:
Bondue A;Tännler S;Chiapparo G;Chabab S;Ramialison M;Paulissen C;Beck B;Harvey R;Blanpain C

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Mesp1 是体内心血管发育的最早标志物,用于分离和表征 ESC 分化过程中的多能心血管祖细胞。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由两种类型的多能心血管祖细胞(MCP)产生,即第一心区和第二心区。一个关键问题是这两个 MCP 群体是否由共同祖先的分化产生。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 细胞富含 MCP,具有在体外和体内从心脏区域分化为多种心血管谱系的能力。 Mesp1-GFP 细胞的转录分析发现了 MCP 表达的细胞表面标记,从而可以进行前瞻性分离。 Mesp1 是 MCP 规范和关键心血管转录因子表达所必需的。 Isl1 在早期表达 Mesp1 的细胞亚群中独立于 Mesp1 表达,并与 Mesp1 共同作用促进心血管分化。我们的研究确定了 ESC 分化过程中位于心血管谱系细胞层次顶部的早期 MCP。
Mesp1, the earliest marker of cardiovascular development in vivo, is used to isolate and characterize multipotent cardiovascular progenitors during ESC differentiation. 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.
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