Motor cortex transcriptome reveals microglial key events in amyotrophic lateral sclerosis.

Neurology. Neuroimmunology and Neuroinflammation
Oriol Dols-IcardoJordi Clarimon

Abstract

To identify transcriptomic changes, neuropathologic correlates, and cellular subpopulations in the motor cortex of sporadic amyotrophic lateral sclerosis (ALS). We performed massive RNA sequencing of the motor cortex of patients with ALS (n = 11) and healthy controls (HCs; n = 8) and analyzed gene expression alterations, differential isoform usage, and gene coexpression networks. Furthermore, we used cell type deconvolution algorithms with human single-nucleus RNA sequencing data as reference to identify perturbations in cell type composition associated with ALS. We performed immunohistochemical techniques to evaluate neuropathologic changes in this brain region. We report extensive RNA expression alterations at gene and isoform levels, characterized by the enrichment of neuroinflammatory and synaptic-related pathways. The assembly of gene coexpression modules confirmed the involvement of these 2 major transcriptomic changes, which also showed opposite directions related to the disease. Cell type deconvolution revealed an overrepresentation of microglial cells in ALS compared with HC. Notably, microgliosis was driven by a subcellular population presenting a gene expression signature overlapping with the recently described disea...Continue Reading

References

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Citations

Dec 15, 2020·Journal of Neurochemistry·Nofar Stolero, Dan Frenkel
Oct 30, 2020·International Journal of Molecular Sciences·Giada CipollinaMarco Peviani
Jan 12, 2021·Brain : a Journal of Neurology·Benjamin E Clarke, Rickie Patani
Apr 24, 2021·Neuroscience Letters·Laura Ferraiuolo, Nicholas J Maragakis
May 20, 2021·Trends in Neurosciences·Alexandra C M Van HartenSerge Przedborski
Jul 3, 2021·International Journal of Molecular Sciences·Christine Péladeau, Jagdeep K Sandhu
Oct 12, 2021·Frontiers in Neuroscience·Luca MuzioGianvito Martino

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Datasets Mentioned

BETA
EGAS00001004286

Methods Mentioned

BETA
RNAseq
snRNAseq

Software Mentioned

ROSMAP
MATLAB
DESeq2
DESeq2 WGCNA )
MuSiC
R
ggpubr package
WGCNA
bicor
multicrop

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