한빛사논문
- 조회285
Luke C. Dabin1,2 Holly Kersey1,2,3 Byungwook Kim1,2 Dominic J. Acri1,2,3 Daniel Sharify1,2 Audrey Lee-Gosselin2 Cristian A. Lasagna-Reeves2,3,4,5 Adrian L. Oblak2,3,6 Bruce T. Lamb1,2,3 Jungsu Kim1,2,3
1Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA
2Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA
3Medical Neuroscience Graduate Program, Indiana University School of Medicine, Indianapolis, Indiana, USA
4Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
5Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA
6Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA
Luke C. Dabin and Holly Kersey contributed equally to this work.
Correspondence: Jungsu Kim
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 that the normal function of Inpp5d 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.
Highlights: Loss of Inpp5d has different effects in male and female mice. Genes dysregulated by Inpp5d loss relate to neurodegeneration. Total loss of Inpp5d in female mice collapses a conserved gene co-expression module. Loss of microglial Inpp5d affects the transcriptome of other cell types.
논문정보
- Research article
- 2024년 06월 (BRIC 등록일 2024-07-10)
- 국외 연구진
- 생명과학 > 신경생물학
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