Engineering induction of singular neural rosette emergence within hPSC-derived tissues.
Engineering induction of singular neural rosette emergence within hPSC-derived tissues.
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DOI：
10.7554/elife.37549
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发表时间：
2018-10-29
期刊：
影响因子：
7.7
通讯作者：
Ashton RS
中科院分区：
文献类型：
--
作者：
Knight GT;Lundin BF;Iyer N;Ashton LM;Sethares WA;Willett RM;Ashton RS
人类多能干细胞（hPSC）衍生的神经类器官显示出前所未有的涌现特性。然而，与整个中枢神经系统（CNS）在体内发育的单一神经上皮管相反，目前的类器官方案产生具有多个神经上皮单位的组织，也称为神经上皮细胞。神经突起，每个作为独立的形态发生中心，从而混淆协调，可再生的组织发展。在这里，我们发现控制初始组织形态可以有效地（>80%）诱导hPSC衍生的前脑和脊髓组织内的单个神经玫瑰花结出现。值得注意的是，由于先前未知的ROCK介导的细胞收缩性差异，前脑与脊髓组织观察单个玫瑰花结出现的最佳组织形态是不同的。释放后的几何限制，组织表现出放射状的生长与维护一个单一的神经上皮细胞和外周神经元分化。因此，我们已经确定了神经组织形态作为一个关键的生物物理参数，用于控制在体外神经组织形态进一步推进生物制造的CNS组织与仿生解剖学和生理学。
Human pluripotent stem cell (hPSC)-derived neural organoids display unprecedented emergent properties. Yet in contrast to the singular neuroepithelial tube from which the entire central nervous system (CNS) develops in vivo, current organoid protocols yield tissues with multiple neuroepithelial units, a.k.a. neural rosettes, each acting as independent morphogenesis centers and thereby confounding coordinated, reproducible tissue development. Here, we discover that controlling initial tissue morphology can effectively (>80%) induce single neural rosette emergence within hPSC-derived forebrain and spinal tissues. Notably, the optimal tissue morphology for observing singular rosette emergence was distinct for forebrain versus spinal tissues due to previously unknown differences in ROCK-mediated cell contractility. Following release of geometric confinement, the tissues displayed radial outgrowth with maintenance of a singular neuroepithelium and peripheral neuronal differentiation. Thus, we have identified neural tissue morphology as a critical biophysical parameter for controlling in vitro neural tissue morphogenesis furthering advancement towards biomanufacture of CNS tissues with biomimetic anatomy and physiology.