Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest
Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest
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DOI：
10.1016/j.stemcr.2020.07.024
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发表时间：
2020-09-08
影响因子：
5.9
通讯作者：
McCann, Conor J.
中科院分区：
文献类型：
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作者：
Frith, Thomas J. R.;Gogolou, Antigoni;McCann, Conor J.
肠神经系统(ENS)主要起源于迷走神经脊，迷走神经脊是背侧神经管在体节1和7之间形成的一组迁移的多能细胞群。ENS的发育和功能缺陷会导致包括先天性巨结肠在内的一系列肠道神经疾病。对早期ENS前体细胞的信号知之甚少，限制了从人类多能干细胞(HPSCs)生成肠道神经元的进展，从而为肠道神经疾病的疾病建模和再生医学提供了工具。我们描述了从hPSC高效和加速生成ENS前体细胞的过程，揭示了维甲酸对于获得迷走轴身份和早期ENS前体细胞的指定是至关重要的。这些ENS前体细胞在体外产生肠神经元，在体内移植后，在成年小鼠体内实现了ENS的长期定植。因此，hPSC来源的ENS前体细胞可能为ENS缺陷的细胞治疗提供基础。
The enteric nervous system (ENS) is derived primarily from the vagal neural crest, a migratory multipotent cell population emerging from the dorsal neural tube between somites 1 and 7. Defects in the development and function of the ENS cause a range of enteric neuropathies, including Hirschsprung disease. Little is known about the signals that specify early ENS progenitors, limiting progress in the generation of enteric neurons from human pluripotent stem cells (hPSCs) to provide tools for disease modeling and regenerative medicine for enteric neuropathies. We describe the efficient and accelerated generation of ENS progenitors from hPSCs, revealing that retinoic acid is critical for the acquisition of vagal axial identity and early ENS progenitor specification. These ENS progenitors generate enteric neurons in vitro and, following in vivo transplantation, achieved long-term colonization of the ENS in adult mice. Thus, hPSC-derived ENS progenitors may provide the basis for cell therapy for defects in the ENS.