Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Cell Stem Cell. 2013 May 2;12(5):587-601. doi: 10.1016/j.stem.2013.03.004.
Mesp1 is regarded as the master regulator of cardiovascular development, initiating the cardiac transcription factor cascade to direct the generation of cardiac mesoderm. To define the early embryonic cell population that responds to Mesp1, we performed pulse inductions of gene expression over tight temporal windows following embryonic stem cell differentiation. Remarkably, instead of promoting cardiac differentiation in the initial wave of mesoderm, Mesp1 binds to the Tal1 (Scl) +40 kb enhancer and generates Flk-1+ precursors expressing Etv2 (ER71) and Tal1 that undergo hematopoietic differentiation. The second wave of mesoderm responds to Mesp1 by differentiating into PDGFRα+ precursors that undergo cardiac differentiation. Furthermore, in the absence of serum-derived factors, Mesp1 promotes skeletal myogenic differentiation. Lineage tracing revealed that the majority of yolk sac and many adult hematopoietic cells derive from Mesp1+ precursors. Thus, Mesp1 is a context-dependent determination factor, integrating the stage of differentiation and the signaling environment to specify different lineage outcomes.
Mesp1 被认为是心血管发育的主要调节因子，它启动心脏转录因子级联反应，指导心脏中胚层的生成。为了确定对 Mesp1 有反应的早期胚胎细胞群体，我们在胚胎干细胞分化后的紧密时间窗口内进行了基因表达的脉冲诱导。值得注意的是，Mesp1 并没有在中胚层的初始波中促进心脏分化，而是与 Tal1（Scl）+40kb 增强子结合，并产生表达 Etv2（ER71）和 Tal1 的 Flk-1+前体细胞，这些前体细胞经历造血分化。第二波中胚层通过分化为 PDGFRα+前体细胞来响应 Mesp1，这些前体细胞经历心脏分化。此外，在没有血清来源的因子的情况下，Mesp1 促进成肌细胞的分化。谱系追踪显示，大多数卵黄囊和许多成年造血细胞都来源于 Mesp1+前体细胞。因此，Mesp1 是一个依赖于上下文的决定因素，它整合分化阶段和信号环境来指定不同的谱系结果。
