Modeling Hypoxia-Induced Neuropathies Using a Fast and Scalable Human Motor Neuron Differentiation System.
cell compartments
diabetic neuropathies
fractionation
hypoxia
neurites
soma
stem cell-derived human motor neurons
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
09 06 2020
09 06 2020
Historique:
received:
21
10
2019
revised:
07
04
2020
accepted:
08
04
2020
pubmed:
11
5
2020
medline:
20
4
2021
entrez:
11
5
2020
Statut:
ppublish
Résumé
Human motor neuron (MN) diseases encompass a spectrum of disorders. A critical barrier to dissecting disease mechanisms is the lack of appropriate human MN models. Here, we describe a scalable, suspension-based differentiation system to generate functional human MN diseases in 3 weeks. Using this model, we translated recent findings that mRNA mis-localization plays a role in disease development to the human context by establishing a membrane-based system that allows efficient fractionation of MN cell soma and neurites. In response to hypoxia, used to mimic diabetic neuropathies, MNs upregulated mitochondrial transcripts in neurites; however, mitochondria were decreased. These data suggest that hypoxia may disrupt translation of mitochondrial mRNA, potentially leading to neurite damage and development of neuropathies. We report the development of a novel human MN model system to investigate mechanisms of disease affecting soma and/or neurites that facilitates the rapid generation and testing of patient-specific MN diseases.
Identifiants
pubmed: 32386561
pii: S2213-6711(20)30143-0
doi: 10.1016/j.stemcr.2020.04.003
pmc: PMC7355142
pii:
doi:
Substances chimiques
Mitochondrial Proteins
0
RNA, Messenger
0
Oxygen
S88TT14065
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
1033-1043Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM133385
Pays : United States
Organisme : NIDDK NIH HHS
ID : K12 DK094712
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120444
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI140044
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK118803
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002535
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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