Integrative genetic and single cell RNA sequencing analysis provides new clues to the amyotrophic lateral sclerosis neurodegeneration.

ABSTRACT:

Introduction

The gradual loss of motor neurons (MNs) in the brain and spinal cord is a hallmark of amyotrophic lateral sclerosis (ALS), but the mechanisms underlying neurodegeneration in ALS are still not fully understood.

Methods

Based on 75 ALS-pathogenicity/susceptibility genes and large-scale single-cell transcriptomes of human/mouse brain/spinal cord/muscle tissues, we performed an expression enrichment analysis to identify cells involved in ALS pathogenesis. Subsequently, we created a strictness measure to estimate the dosage requirement of ALS-related genes in linked cell types.

Results

Remarkably, expression enrichment analysis showed that α- and γ-MNs, respectively, are associated with ALS-susceptibility genes and ALS-pathogenicity genes, revealing difference

SUBMITTER: Liu H 

PROVIDER: S-EPMC9983639 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature