Modeling Hypoxia-Induced Neuropathies Using a Fast and Scalable Human Motor Neuron Differentiation System
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved..
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.
| Errataetall: |
ErratumIn: Stem Cell Reports. 2021 Apr 13;16(4):1009. - PMID 33852882 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Stem cell reports - 14(2020), 6 vom: 09. Juni, Seite 1033-1043 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hudish, Laura I [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.04.2021 Date Revised 19.04.2021 published: Print-Electronic ErratumIn: Stem Cell Reports. 2021 Apr 13;16(4):1009. - PMID 33852882 Citation Status MEDLINE |
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| doi: |
10.1016/j.stemcr.2020.04.003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM309697727 |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Bubak, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Triolo, Taylor M |e verfasserin |4 aut | |
| 700 | 1 | |a Niemeyer, Christy S |e verfasserin |4 aut | |
| 700 | 1 | |a Lorberbaum, David S |e verfasserin |4 aut | |
| 700 | 1 | |a Sussel, Lori |e verfasserin |4 aut | |
| 700 | 1 | |a Nagel, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Taliaferro, J Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Russ, Holger A |e verfasserin |4 aut | |
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