Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA; Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA; Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA; Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Stem Cell Reports. 2015 Jun 9;4(6):1075-88. doi: 10.1016/j.stemcr.2015.04.013. Epub 2015 May 21.
To gain insight into the cellular and molecular cues that promote neurovascular co-patterning at the earliest stages of human embryogenesis, we developed a human embryonic stem cell model to mimic the developing epiblast. Contact of ectoderm-derived neural cells with mesoderm-derived vasculature is initiated via the neural crest (NC), not the neural tube (NT). Neurovascular co-patterning then ensues with specification of NC toward an autonomic fate requiring vascular endothelial cell (EC)-secreted nitric oxide (NO) and direct contact with vascular smooth muscle cells (VSMCs) via T-cadherin-mediated homotypic interactions. Once a neurovascular template has been established, NT-derived central neurons then align themselves with the vasculature. Our findings reveal that, in early human development, the autonomic nervous system forms in response to distinct molecular cues from VSMCs and ECs, providing a model for how other developing lineages might coordinate their co-patterning.
为了深入了解在人类胚胎发生的最早阶段促进神经血管共构的细胞和分子线索，我们开发了一种人类胚胎干细胞模型来模拟发育中的上胚层。外胚层衍生的神经细胞与中胚层衍生的脉管系统的接触是通过神经嵴（NC）而不是神经管（NT）开始的。随后，随着 NC 向自主命运的特化，神经血管共构发生，这需要血管内皮细胞（EC）分泌的一氧化氮（NO）和通过 T-钙粘蛋白介导的同质相互作用与血管平滑肌细胞（VSMCs）直接接触。一旦建立了神经血管模板，NT 衍生的中枢神经元就会与脉管系统对齐。我们的发现表明，在人类早期发育中，自主神经系统是对来自 VSMCs 和 EC 的不同分子线索的反应而形成的，为其他发育谱系如何协调它们的共构提供了模型。
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