{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wu HF"],"funding":["National Institute of Neurological Disorders and Stroke","NICHD NIH HHS","NHLBI NIH HHS","NINDS NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["734-753.e8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11069445"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(5)"],"pubmed_abstract":["Autonomic parasympathetic neurons (parasymNs) control unconscious body responses, including \"rest-and-digest.\" ParasymN innervation is important for organ development, and parasymN dysfunction is a hallmark of autonomic neuropathy. However, parasymN function and dysfunction in humans are vastly understudied due to the lack of a model system. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as a versatile platform. Here, we developed a differentiation paradigm detailing the derivation of functional human parasymNs from Schwann cell progenitors. We employ these neurons (1) to assess human autonomic nervous system (ANS) development, (2) to model neuropathy in the genetic disorder familial dysautonomia (FD), (3) to show parasymN dysfunction during SARS-CoV-2 infection, (4) to model the autoimmune disease Sjögren's syndrome (SS), and (5) to show that parasymNs innervate white adipocytes (WATs) during development and promote WAT maturation. Our model system could become instrumental for future disease modeling and drug discovery studies, as well as for human developmental studies."],"journal":["Cell stem cell"],"pubmed_title":["Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development."],"pmcid":["PMC11069445"],"funding_grant_id":["18/503,100","1R21HD106118-01","R01 HL173931","R01 GM107092","R21 HD106118","R01 NS114567","1R01NS114567-01A1","R01 GM105772"],"pubmed_authors":["Seo DE","Zeltner N","McAlpine JL","Ivanova NB","Santori FR","Chen YW","Krishnaswamy S","Ishan M","Liu HX","Huang CW","Hart GW","Magruder DS","Bergeron HC","Saito-Diaz K","Delaney WH","Wu HF","Hogan RJ"],"additional_accession":[]},"is_claimable":false,"name":"Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development.","description":"Autonomic parasympathetic neurons (parasymNs) control unconscious body responses, including \"rest-and-digest.\" ParasymN innervation is important for organ development, and parasymN dysfunction is a hallmark of autonomic neuropathy. However, parasymN function and dysfunction in humans are vastly understudied due to the lack of a model system. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as a versatile platform. Here, we developed a differentiation paradigm detailing the derivation of functional human parasymNs from Schwann cell progenitors. We employ these neurons (1) to assess human autonomic nervous system (ANS) development, (2) to model neuropathy in the genetic disorder familial dysautonomia (FD), (3) to show parasymN dysfunction during SARS-CoV-2 infection, (4) to model the autoimmune disease Sjögren's syndrome (SS), and (5) to show that parasymNs innervate white adipocytes (WATs) during development and promote WAT maturation. Our model system could become instrumental for future disease modeling and drug discovery studies, as well as for human developmental studies.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-01T05:53:20.09Z","creation":"2025-07-08T03:13:28.595Z"},"accession":"S-EPMC11069445","cross_references":{"pubmed":["38608707"],"doi":["10.1016/j.stem.2024.03.011"]}}