Human axial progenitors generate trunk neural crest cells in vitro.
Human axial progenitors generate trunk neural crest cells in vitro.
复制标题
DOI：
10.7554/elife.35786
复制
发表时间：
2018-08-10
期刊：
影响因子：
7.7
通讯作者：
Tsakiridis A
中科院分区：
文献类型：
--
作者：
Frith TJ;Granata I;Wind M;Stout E;Thompson O;Neumann K;Stavish D;Heath PR;Ortmann D;Hackland JO;Anastassiadis K;Gouti M;Briscoe J;Wilson V;Johnson SL;Placzek M;Guarracino MR;Andrews PW;Tsakiridis A
神经嵴（NC）是一个多能胚胎细胞群，以轴向位置依赖的方式产生不同的细胞类型。从人多能干细胞（hPSC）生产NC细胞是研究人NC生物学的有价值的方法。然而，人躯干NC的起源仍然不明确，目前的体外分化策略诱导的躯干NC细胞的产量有限。在这里，我们表明，hPSC衍生的轴向祖细胞，位于后方的驱动程序的胚胎轴伸长，产生干NC细胞及其衍生物。此外，我们定义的分子签名与不同的轴向身份的人NC细胞在体外的出现。总的来说，我们的研究结果表明，有两种途径对人类颅后NC状态：心脏和迷走神经NC的诞生是促进视黄酸诱导的posteriorisation的前体，而躯干NC出现在池中的后轴祖细胞。
The neural crest (NC) is a multipotent embryonic cell population that generates distinct cell types in an axial position-dependent manner. The production of NC cells from human pluripotent stem cells (hPSCs) is a valuable approach to study human NC biology. However, the origin of human trunk NC remains undefined and current in vitro differentiation strategies induce only a modest yield of trunk NC cells. Here we show that hPSC-derived axial progenitors, the posteriorly-located drivers of embryonic axis elongation, give rise to trunk NC cells and their derivatives. Moreover, we define the molecular signatures associated with the emergence of human NC cells of distinct axial identities in vitro. Collectively, our findings indicate that there are two routes toward a human post-cranial NC state: the birth of cardiac and vagal NC is facilitated by retinoic acid-induced posteriorisation of an anterior precursor whereas trunk NC arises within a pool of posterior axial progenitors.