Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development

Hsueh Fu Wu, Kenyi Saito-Diaz, Chia Wei Huang, Jessica L. McAlpine, Dong Eun Seo, D. Sumner Magruder, Mohamed Ishan, Harrison C. Bergeron, William H. Delaney, Fabio R. Santori, Smita Krishnaswamy, Gerald W. Hart, Ya Wen Chen, Robert J. Hogan, Hong Xiang Liu, Natalia B. Ivanova, Nadja Zeltner

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish
Pages (from-to)734-753.e8
JournalCell Stem Cell
Volume31
Issue number5
DOIs
StatePublished - 2 May 2024

Keywords

  • COVID-19
  • Schwann cell progenitors
  • Sjögren's syndrome
  • adipocyte innervation
  • autonomic nervous system
  • disease modeling
  • familial dysautonomia
  • human pluripotent stem cells
  • parasympathetic neurons
  • peripheral nervous system

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