Development of Bipotent Cardiac/Skeletal Myogenic Progenitors from MESP1+ Mesoderm.
Development of Bipotent Cardiac/Skeletal Myogenic Progenitors from MESP1+ Mesoderm.
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DOI：
10.1016/j.stemcr.2015.12.003
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发表时间：
2016-01-12
影响因子：
5.9
通讯作者：
Kyba M
中科院分区：
文献类型：
--
作者：
Chan SS;Hagen HR;Swanson SA;Stewart R;Boll KA;Aho J;Thomson JA;Kyba M
鳃骨骨骼肌与新的心室共同进化，使脊索动物能够进行捕食。这些共同进化的组织由前内脏中胚层的共同群体发育而来，称为心咽中胚层（CPM）。人们对CPM的监管和发展知之甚少。我们描述了一种基于胚胎干细胞的系统，其中 MESP1 驱动具有心脏和骨骼肌双重分化潜力以及类似于 CPM 的基因表达的 PDGFRA+ 群体。使用该系统，我们研究了这些双能祖细胞的调节，并发现心脏规格由拮抗性 TGFβ-BMP 轴控制，而骨骼肌规格则通过 Rho 激酶抑制而增强。我们定义了第一个定向 CPM 衍生的心脏和骨骼肌原祖细胞的转录特征，并发现了区分心脏 (PODXL+) 和骨骼肌 (CDH4+) CPM 衍生物的表面标记。这些工具为了解这个在发育和进化上重要的群体打开了一个可访问的窗口。 MESP1 诱导双能 PDGFRA+ 心脏/骨骼肌源性祖细胞 MESP1+ PDGFRA+ 细胞在功能上类似于心咽中胚层 (CPM) TGFβ-BMP 和 Rho 激酶信号传导调节 CPM 谱系选择 PODXL 和 CDH4 标记早期心脏和骨骼肌源性祖细胞 在本文中，Kyba 及其同事证明，双能 PDGFRA+ 心脏/骨骼肌源性祖细胞群功能类似于心咽中胚层 (CPM) 的细胞可以由体外分化的 ES 细胞产生。他们发现 TGFβ-BMP 和 Rho 激酶信号传导调节 CPM 分化，并将 PODXL 和 CDH4 分别鉴定为最早的心脏和骨骼肌源性祖细胞的表面标记。
The branchiomeric skeletal muscles co-evolved with new chambers of the heart to enable predatory feeding in chordates. These co-evolved tissues develop from a common population in anterior splanchnic mesoderm, referred to as cardiopharyngeal mesoderm (CPM). The regulation and development of CPM are poorly understood. We describe an embryonic stem cell-based system in which MESP1 drives a PDGFRA+ population with dual cardiac and skeletal muscle differentiation potential, and gene expression resembling CPM. Using this system, we investigate the regulation of these bipotent progenitors, and find that cardiac specification is governed by an antagonistic TGFβ-BMP axis, while skeletal muscle specification is enhanced by Rho kinase inhibition. We define transcriptional signatures of the first committed CPM-derived cardiac and skeletal myogenic progenitors, and discover surface markers to distinguish cardiac (PODXL+) from the skeletal muscle (CDH4+) CPM derivatives. These tools open an accessible window on this developmentally and evolutionarily important population. MESP1 induces bipotent PDGFRA+ cardiac/skeletal myogenic progenitors MESP1+ PDGFRA+ cells functionally resemble cardiopharyngeal mesoderm (CPM) TGFβ-BMP and Rho kinase signaling regulate CPM lineage choice PODXL and CDH4 mark early cardiac and skeletal myogenic-committed progenitors In this article, Kyba and colleagues demonstrate that a bipotent PDGFRA+ cardiac/skeletal myogenic progenitor population functionally resembling cardiopharyngeal mesoderm (CPM) can be generated from ES cells differentiated in vitro. They find that TGFβ-BMP and Rho kinase signaling regulate CPM differentiation, and identify PODXL and CDH4 as surface markers for the earliest cardiac and skeletal myogenic-committed progenitors, respectively.