{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Fan Y"],"funding":["NIDDK NIH HHS","NIA NIH HHS","NCI NIH HHS","NINDS NIH HHS"],"pagination":["264-282.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10034921"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(3)"],"pubmed_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."],"journal":["Cell stem cell"],"pubmed_title":["hPSC-derived sacral neural crest enables rescue in a severe model of Hirschsprung's disease."],"pmcid":["PMC10034921"],"funding_grant_id":["F31 AG067709","R01 NS099270","P30 CA008748","F32 DK132810","R01 DK126644","R01 DK130517","R01 NS015547"],"pubmed_authors":["Baggiolini A","Minotti AP","Hung LY","Zhong A","Fan Y","Oberst P","Sidharta M","Studer L","Margolis KG","Zumbo P","Zhou T","Najjar S","Hackland J","Hergenreder E","de Stanchina E","Huang Z","Gershon M","Cruz NM","Betel D","White RM","Zhao H"],"additional_accession":[]},"is_claimable":false,"name":"hPSC-derived sacral neural crest enables rescue in a severe model of Hirschsprung's disease.","description":"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.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Mar","modification":"2024-10-16T07:33:18.39Z","creation":"2024-10-16T07:33:18.39Z"},"accession":"S-EPMC10034921","cross_references":{"pubmed":["36868194"],"doi":["10.1016/j.stem.2023.02.003"]}}