State University of New York Polytechnic Institute, College of Nanoscale Science and Engineering, Nanobioscience Constellation, Albany, NY, USA.
Nat Commun. 2021 May 21;12(1):3020. doi: 10.1038/s41467-021-23294-7.
Stem cell technologies including self-assembling 3D tissue models provide access to early human neurodevelopment and fundamental insights into neuropathologies. Gastruloid models have not been used to investigate co-developing central and peripheral neuronal systems with trunk mesendoderm which we achieve here in elongating multi-lineage organized (EMLO) gastruloids. We evaluate EMLOs over a forty-day period, applying immunofluorescence of multi-lineage and functional biomarkers, including day 16 single-cell RNA-Seq, and evaluation of ectodermal and non-ectodermal neural crest cells (NCCs). We identify NCCs that differentiate to form peripheral neurons integrated with an upstream spinal cord region after day 8. This follows initial EMLO polarization events that coordinate with endoderm differentiation and primitive gut tube formation during multicellular spatial reorganization. This combined human central-peripheral nervous system model of early organogenesis highlights developmental events of mesendoderm and neuromuscular trunk regions and enables systemic studies of tissue interactions and innervation of neuromuscular, enteric and cardiac relevance.
干细胞技术包括自组装的 3D 组织模型，为研究早期人类神经发育和神经病理学的基本原理提供了途径。类囊胚模型尚未用于研究与躯干中胚层共同发育的中枢和周围神经元系统，而我们在这里通过延长多谱系组织（EMLO）类囊胚实现了这一目标。我们在 40 天的时间内评估 EMLO，应用多谱系和功能生物标志物的免疫荧光技术，包括第 16 天的单细胞 RNA-Seq，并评估外胚层和非外胚层神经嵴细胞（NCC）。我们发现 NCC 在第 8 天后分化为外周神经元，并与上游脊髓区域整合。这是在多细胞空间重组过程中，伴随着内胚层分化和原始肠道管形成的初始 EMLO 极化事件发生的。这种早期器官发生的人中枢-外周神经系统模型突出了中胚层和神经肌肉躯干区域的发育事件，并能够对组织相互作用和神经肌肉、肠和心脏相关的神经支配进行系统研究。
