<br>hPSC 衍生的骶神经嵴能够挽救严重的先天性巨结肠模型,Cell Stem Cell

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hPSC 衍生的骶神经嵴能够挽救严重的先天性巨结肠模型
Cell Stem Cell ( IF 19.8 ) Pub Date : 2023-03-02 , DOI: 10.1016/j.stem.2023.02.003
Yujie Fan ₁ , James Hackland ₂ , Arianna Baggiolini ₂ , Lin Y Hung ₃ , Huiyong Zhao ₄ , Paul Zumbo ₅ , Polina Oberst ₂ , Andrew P Minotti ₁ , Emiliano Hergenreder ₁ , Sarah Najjar ₃ , Zixing Huang ₃ , Nelly M Cruz ₆ , Aaron Zhong ₇ , Mega Sidharta ₇ , Ting Zhou ₇ , Elisa de Stanchina ₄ , Doron Betel ₈ , Richard M White ₆ , Michael Gershon ₉ , Kara Gross Margolis ₁₀ , Lorenz Studer ₂

Affiliation

The Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065, USA.
The Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA.
Antitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA; Applied Bioinformatics Core, Weill Cornell Medicine, New York, NY 10065, USA.
Cancer Biology and Genetics and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
The Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; The SKI Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Applied Bioinformatics Core, Weill Cornell Medicine, New York, NY 10065, USA; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA; Department of Pediatrics, NYU Grossman School of Medicine, New York, NY 10010, USA.

肠神经系统（ENS）源自神经嵴（NC）的迷走神经和骶神经部分。在这里，我们提出了通过定时暴露于 FGF、WNT 和 GDF11，从人类 PSC 衍生出骶骨 ENS 前体，这分别实现了后部模式化和从后躯干到骶骨 NC 身份的转变。使用SOX2 ::H2B-tdTomato/ T ::H2B-GFP 双报告 hPSC 系，我们证明躯干和骶神经 NC 均来自双阳性神经中胚层祖细胞 (NMP)。迷走神经和骶神经 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，需要迷走神经和骶神经 NC 谱系的异种移植来拯救完全无神经节病的小鼠模型，这表明有机会治疗严重的先天性巨结肠症。

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更新日期：2023-03-02

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