hPSC-derived sacral neural crest enables rescue in a severe model of Hirschsprung's disease
Summary
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. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
| Authors | Fan Y, Hackland J, Baggiolini A, Hung LY, Zhao H, Zumbo P, Oberst P, Minotti AP, Hergenreder E, Najjar S, Huang Z, Cruz NM, Zhong A, Sidharta M, Zhou T, de Stanchina E, Betel D, White RM, Gershon M, Margolis KG, Studer L |
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| Journal | Cell stem cell |
| Publication Date | 2023 Mar 2;30(3):264-282.e9 |
| PubMed | 36868194 |
| PubMed Central | PMC10034921 |
| DOI | 10.1016/j.stem.2023.02.003 |
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