Loss of Inpp5d has disease-relevant and sex-specific effects on glial transcriptomes.

ABSTRACT:

Introduction

Inpp5d is genetically associated with Alzheimer's disease risk. Loss of Inpp5d alters amyloid pathology in models of amyloidosis. Inpp5d is expressed predominantly in microglia but its function in brain is poorly understood.

Methods

We performed single-cell RNA sequencing to study the effect of Inpp5d loss on wild-type mouse brain transcriptomes.

Results

Loss of Inpp5d has sex-specific effects on the brain transcriptome. Affected genes are enriched for multiple neurodegeneration terms. Network analyses reveal a gene co-expression module centered around Inpp5d in female mice. Inpp5d loss alters Pleotrophin (PTN), Prosaposin (PSAP), and Vascular Endothelial Growth Factor A (VEGFA) signaling probability between cell types.

Discussion

Our data suggest

SUBMITTER: Dabin LC 

PROVIDER: S-EPMC11350029 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature