Spinal Muscular Atrophy Patient iPSC-Derived Motor Neurons Have Reduced Expression of Proteins Important in Neuronal Development

Frontiers in Cellular Neuroscience
Heidi R FullerDhruv Sareen

Abstract

Spinal muscular atrophy (SMA) is an inherited neuromuscular disease primarily characterized by degeneration of spinal motor neurons, and caused by reduced levels of the SMN protein. Previous studies to understand the proteomic consequences of reduced SMN have mostly utilized patient fibroblasts and animal models. We have derived human motor neurons from type I SMA and healthy controls by creating their induced pluripotent stem cells (iPSCs). Quantitative mass spectrometry of these cells revealed increased expression of 63 proteins in control motor neurons compared to respective fibroblasts, whereas 30 proteins were increased in SMA motor neurons vs. their fibroblasts. Notably, UBA1 was significantly decreased in SMA motor neurons, supporting evidence for ubiquitin pathway defects. Subcellular distribution of UBA1 was predominantly cytoplasmic in SMA motor neurons in contrast to nuclear in control motor neurons; suggestive of neurodevelopmental abnormalities. Many of the proteins that were decreased in SMA motor neurons, including beta III-tubulin and UCHL1, were associated with neurodevelopment and differentiation. These neuron-specific consequences of SMN depletion were not evident in fibroblasts, highlighting the importance o...Continue Reading

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Citations

May 24, 2018·Human Molecular Genetics·Ewout J N GroenThomas H Gillingwater
Apr 15, 2020·Neuroscience Insights·Darija Šoltić, Heidi R Fuller
Jun 13, 2020·Frontiers in Cell and Developmental Biology·Anna SlanziGabriela Constantin
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Datasets Mentioned

BETA
GMO3814
GMO0232
GM00232
GM03814

Methods Mentioned

BETA
SMA
protein assay
electrophoresis
biopsies
transgenic

Software Mentioned

Image J
Database for Annotation , Visualization and Integrated Discove...
Excel
Plotly
ProteinPilot
PluriTest
ImageJ
Graphpad Prism
ABSciex

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