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Status |
Public on Jun 26, 2024 |
Title |
Loss of Inpp5d has disease-relevant and sex-specific effects on glial transcriptomes |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
INTRODUCTION: INPP5D is genetically associated with Alzheimer’s disease risk. Loss of Inpp5d alters amyloid pathology in models of amyloidosis. Inpp5d is predominantly expressed 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 PTN, PSAP, and VEGFA signaling probability between cell types. DISCUSSION: Our data suggest Inpp5d’s normal function is entangled with mechanisms involved in neurodegeneration. We report the effect of Inpp5d loss without pathology and show that this has dramatic effects on gene expression. Our study provides a critical reference for researchers of neurodegeneration, allowing separation of disease-specific changes mediated by Inpp5d in disease from baseline effects of Inpp5d loss.
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Overall design |
Data contains single-cell RNA-sequencing data from two female and male wildtype, two female and male Inpp5d hetereozygous knockout, two female and male Inpp5d homozygous knockout mice, all six weeks of age.
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Web link |
https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.13901
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Contributor(s) |
Dabin LC, Kersey H, Kim B, Acri DJ, Sharify AD, Lee-Gosselin A, Lasagna-Reeves CA, Oblak A, Lamb BT, Kim J |
Citation(s) |
38923164 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
R01 AG077829 |
Molecular genetic analyses of transcriptional dysregulation in Alzheimers disease |
INDIANA UNIVERSITY |
Jungsu Kim |
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Submission date |
Feb 03, 2024 |
Last update date |
Sep 26, 2024 |
Contact name |
Luke Child Dabin |
Organization name |
Indiana University
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Department |
Medical and Molecular Genetics
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Lab |
Jungsu Kim
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Street address |
320 W 15th St #414
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City |
Indianapolis |
State/province |
Indiana |
ZIP/Postal code |
46202 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (12)
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Relations |
BioProject |
PRJNA1072999 |
Supplementary file |
Size |
Download |
File type/resource |
GSE254999_RAW.tar |
2.4 Gb |
(http)(custom) |
TAR (of TAR) |
SRA Run Selector |
Raw data are available in SRA |
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