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Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest.
Stem Cell Reports ( IF 5.9 ) Pub Date : 2020-08-27 , DOI: 10.1016/j.stemcr.2020.07.024
Thomas J R Frith 1 , Antigoni Gogolou 1 , James O S Hackland 2 , Zoe A Hewitt 1 , Harry D Moore 1 , Ivana Barbaric 1 , Nikhil Thapar 3 , Alan J Burns 4 , Peter W Andrews 1 , Anestis Tsakiridis 1 , Conor J McCann 5
Affiliation  

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.



中文翻译:

视黄酸加速了源自体外神经C的肠神经祖细胞的规格。

肠神经系统(ENS)主要来自迷走神经rest,迷走神经c是从1号和7号躯干之间的背侧神经管涌出的迁移性多能细胞群。ENS的发育和功能缺陷会导致一系列肠道神经病,包括巨结肠疾病。关于指定早期ENS祖细胞的信号知之甚少,这些信号限制了人类多能干细胞(hPSC)产生肠道神经元的进展,从而为疾病建模和用于肠道神经病的再生医学提供了工具。我们描述了从hPSCs产生ENS祖细胞的有效和加速过程,揭示了视黄酸对于迷走神经轴向身份和早期ENS祖细胞规范的获取至关重要。这些ENS祖细胞在体外产生肠神经元并且在体内移植后,在成年小鼠中实现了ENS的长期定居。因此,hPSC衍生的ENS祖细胞可为ENS缺陷的细胞治疗提供基础。

更新日期:2020-08-27
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