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A study of how homozygous ALS-linked FUS P525L mutations perturb transcriptome profile in human iPSC-derived microglia

ABSTRACT: Purpose: The FUS P525L mutation is highly penetrant and causes ALS cases with earlier disease onset and more aggressive progression. This study aims to understand the impact of P525L mutations in microglia during ALS pathogenesis. We compare the transcriptome (RNA-seq) of P525L mutations to the wildtype and isogenic controls to derive the differentially perturbed genes. Methods: Transcriptome profiles of human iPSC-derived microglia with gentoype of wild-type (WT), isogenic control (eCtrl), P525L homozygous (P525LHom), P525L heterozygous (P252LHet) and null deletion (KO) were generated using Illumina HiSeq2000 by multiplexed paired-read run with 100 cycles. Pass-QC sequencing reads were mapped to the human genome (hg19) using the OmicSoft ArrayStudio software followed by differential gene expression analysis via DESeq2 package. Results: Homozygous P525L mutations perturb the transcriptome profile where many differentially expressed genes are associated with microglial functions. Specifically, dysregulation of several chemoreceptor genes leads to altered chemoreceptor-activated calcium signaling. Conclusions: Our study underscores the cell- autonomous effects of the ALS-linked FUS P525L mutation in a human microglia model.

ORGANISM(S): Homo sapiens

PROVIDER: GSE172459 | GEO | 2022/02/03

REPOSITORIES: GEO

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Activation of polo-like kinase 1 expression in spinal motor neurons as vulnerability factor of spinal motor neurons in FUS- and other fALS

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Project description:A study of how homozygous ALS-linked FUS P525L mutations perturb transcriptome profile in human iPSC-derived microglia

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