美国纪念斯隆凯特琳癌症中心干细胞生物学中心Lorenz Studer研究团队发现hPSC来源的骶骨神经嵴（NC）能够挽救严重的先天性巨结肠模型。2023年3月2日出版的《细胞—干细胞》杂志发表了这一最新研究成果。

他们介绍了通过定时暴露于FGF、WNT和GDF11从人类PSC来源的骶部肠神经系统 （ENS）前体，这分别实现了后模式和从后躯干到NC身份的过渡。使用SOX2::H2B-tdTomato / T::H2B-GFP双报告基因hPSC系，他们证明了躯干和骶骨NC都来自双阳性神经-中胚层祖细胞（NMP）。迷走神经和骶骨NC前体在体外和体内产生不同的神经元亚型和迁移行为。

值得注意的是，需要迷走神经和骶部NC谱系的异种移植来挽救全神经节垂死症的小鼠模型，这表明严重的先天性巨结肠将有治疗机会。

附：英文原文

Title: hPSC-derived sacral neural crest enables rescue in a severe model of Hirschsprung’s disease

Author: Yujie Fan, James Hackland, Arianna Baggiolini, Lin Y. Hung, Huiyong Zhao, Paul Zumbo, Polina Oberst, Andrew P. Minotti, Emiliano Hergenreder, Sarah Najjar, Zixing Huang, Nelly M. Cruz, Aaron Zhong, Mega Sidharta, Ting Zhou, Elisa de Stanchina, Doron Betel, Richard M. White, Michael Gershon, Kara Gross Margolis, Lorenz Studer

Issue&Volume: 2023/03/02

Abstract: The enteric nervous system (ENS) is derived from both the vagal and sacral component of the neural crest (NC). Here, we present the derivation of sacral ENS precursors from human PSCs via timed exposure to FGF, WNT, and GDF11, which enables posterior patterning and transition from posterior trunk to sacral NC identity, respectively. Using a SOX2::H2B-tdTomato/T::H2B-GFP dual reporter hPSC line, we demonstrate that both trunk and sacral NC emerge from a double-positive neuro-mesodermal progenitor (NMP). Vagal and sacral NC precursors yield distinct neuronal subtypes and migratory behaviors in vitro and in vivo. Remarkably, xenografting of both vagal and sacral NC lineages is required to rescue a mouse model of total aganglionosis, suggesting opportunities in the treatment of severe forms of Hirschsprung’s disease.

DOI: 10.1016/j.stem.2023.02.003

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00040-1