Human VCP mutant ALS/FTD microglia display immune and lysosomal phenotypes independently of GPNMB.

ABSTRACT:

Background

Microglia play crucial roles in maintaining neuronal homeostasis but have been implicated in contributing to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the role of microglia in ALS/FTD remains incompletely understood.

Methods

Here, we generated highly enriched cultures of VCP mutant microglia derived from human induced pluripotent stem cells (hiPSCs) to investigate their cell autonomous and non-cell autonomous roles in ALS pathogenesis. We used RNA-sequencing, proteomics and functional assays to study hiPSC derived VCP mutant microglia and their effects on hiPSC derived motor neurons and astrocytes.

Results

Transcriptomic, proteomic and functional analyses revealed immune and lysosomal dysfunction in VCP mutant microglia

SUBMITTER: Clarke BE 

PROVIDER: S-EPMC11590569 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature