hPSC-derived sacral neural crest enables rescue in a severe model of Hirschsprung's disease Journal Article
| Authors: | Fan, Y.; Hackland, J.; Baggiolini, A.; Hung, L. Y.; Zhao, H.; Zumbo, P.; Oberst, P.; Minotti, A. P.; Hergenreder, E.; Najjar, S.; Huang, Z.; Cruz, N. M.; Zhong, A.; Sidharta, M.; Zhou, T.; de Stanchina, E.; Betel, D.; White, R. M.; Gershon, M.; Margolis, K. G.; Studer, L. |
| Article Title: | hPSC-derived sacral neural crest enables rescue in a severe model of Hirschsprung's disease |
| 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. © 2023 The Authors |
| Keywords: | mouse; animal; animals; mice; bone morphogenetic protein; disease model; xenograft; histone; cell therapy; neural crest; pluripotent stem cells; disease models, animal; histones; enteric nervous system; bone morphogenetic proteins; directed differentiation; regenerative medicine; sacral neural crest; nervous system disorder; neural crest development; humans; human; hirschsprung's disease; hirschsprung disease; heterografts; growth differentiation factor; axial patterning; growth differentiation factors; gdf11 protein, human; gdf11 protein, mouse; axial progenitors; gdf11 |
| Journal Title: | Cell Stem Cell |
| Volume: | 30 |
| Issue: | 3 |
| ISSN: | 1934-5909 |
| Publisher: | Cell Press |
| Date Published: | 2023-03-02 |
| Start Page: | 264 |
| End Page: | 282.e9 |
| Language: | English |
| DOI: | 10.1016/j.stem.2023.02.003 |
| PUBMED: | 36868194 |
| PROVIDER: | scopus |
| PMCID: | PMC10034921 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Lorenz Studer -- Source: Scopus |
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