Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development.
Cell Stem Cell
; 31(5): 734-753.e8, 2024 May 02.
Article
en En
| MEDLINE
| ID: mdl-38608707
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Disautonomía Familiar
/
Diferenciación Celular
/
Células Madre Pluripotentes
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Stem Cell
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos