Modeling Hypoxia-Induced Neuropathies Using a Fast and Scalable Human Motor Neuron Differentiation System

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2020 May 11

PMID 32386561

Citations 6

Authors

Laura I Hudish

Andrew Bubak

Taylor M Triolo

Christy S Niemeyer

David S Lorberbaum

Lori Sussel

Maria Nagel

J Matthew Taliaferro

Holger A Russ

Affiliations

Soon will be listed here.

Abstract

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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