1] Department of Cell and Developmental Biology, South Goodwin Avenue, Urbana, Illinois 61801, USA [2] Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Department of Molecular Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Nat Commun. 2014 Mar 13;5:3449. doi: 10.1038/ncomms4449.
Efficient derivation of large-scale motor neurons (MNs) from human pluripotent stem cells is central to the understanding of MN development, modelling of MN disorders in vitro and development of cell-replacement therapies. Here we develop a method for rapid (20 days) and highly efficient (~70%) differentiation of mature and functional MNs from human pluripotent stem cells by tightly modulating neural patterning temporally at a previously undefined primitive neural progenitor stage. This method also allows high-yield (>250%) MN production in chemically defined adherent cultures. Furthermore, we show that Islet-1 is essential for formation of mature and functional human MNs, but, unlike its mouse counterpart, does not regulate cell survival or suppress the V2a interneuron fate. Together, our discoveries improve the strategy for MN derivation, advance our understanding of human neural specification and MN development, and provide invaluable tools for human developmental studies, drug discovery and regenerative medicine.
高效地从人类多能干细胞中诱导出大量运动神经元（MNs），对于理解 MN 的发育、在体外对 MN 疾病进行建模以及开发细胞替代疗法至关重要。在这里，我们通过在以前未定义的原始神经祖细胞阶段在时间上严格调控神经模式，开发了一种快速（20 天）且高效（~70%）分化成熟和功能 MNs 的方法。该方法还允许在化学定义的贴壁培养物中以高产量（>250%）产生 MN。此外，我们表明，Islet-1 对于形成成熟和功能的人类 MN 是必不可少的，但与它的小鼠对应物不同，它不调节细胞存活或抑制 V2a 中间神经元命运。总之，我们的发现改进了 MN 诱导策略，促进了我们对人类神经特化和 MN 发育的理解，并为人类发育研究、药物发现和再生医学提供了宝贵的工具。
