Human sensorimotor organoids derived from healthy and amyotrophic lateral sclerosis stem cells form neuromuscular junctions.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 08 2021
06 08 2021
Historique:
received:
05
10
2020
accepted:
06
07
2021
entrez:
7
8
2021
pubmed:
8
8
2021
medline:
24
8
2021
Statut:
epublish
Résumé
Human induced pluripotent stem cells (iPSC) hold promise for modeling diseases in individual human genetic backgrounds and thus for developing precision medicine. Here, we generate sensorimotor organoids containing physiologically functional neuromuscular junctions (NMJs) and apply the model to different subgroups of amyotrophic lateral sclerosis (ALS). Using a range of molecular, genomic, and physiological techniques, we identify and characterize motor neurons and skeletal muscle, along with sensory neurons, astrocytes, microglia, and vasculature. Organoid cultures derived from multiple human iPSC lines generated from individuals with ALS and isogenic lines edited to harbor familial ALS mutations show impairment at the level of the NMJ, as detected by both contraction and immunocytochemical measurements. The physiological resolution of the human NMJ synapse, combined with the generation of major cellular cohorts exerting autonomous and non-cell autonomous effects in motor and sensory diseases, may prove valuable to understand the pathophysiological mechanisms of ALS.
Identifiants
pubmed: 34362895
doi: 10.1038/s41467-021-24776-4
pii: 10.1038/s41467-021-24776-4
pmc: PMC8346474
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4744Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK043351
Pays : United States
Organisme : NINDS NIH HHS
ID : DP2 NS106664
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK057521
Pays : United States
Organisme : NINDS NIH HHS
ID : K08 NS082364
Pays : United States
Organisme : NINDS NIH HHS
ID : F32 NS114319
Pays : United States
Informations de copyright
© 2021. The Author(s).
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