Journal article
A glial circadian gene expression atlas reveals cell-type and disease-specific reprogramming in response to amyloid pathology or aging
Nature neuroscience, v 28(11), pp 2366-2379
01 Nov 2025
PMID: 41131361
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
While circadian rhythm disruption may promote neurodegenerative disease, the impact of aging and neurodegenerative pathology on circadian gene expression patterns in different brain cell types remains unknown. Here we used a translating ribosome affinity purification to identify the circadian translatomes of astrocytes, microglia and bulk tissue in healthy mouse cortex and in the settings of amyloid-beta plaque pathology or aging. We show that glial circadian translatomes are highly cell-type-specific and exhibit profound, context-dependent reprogramming in response to amyloid pathology or aging. Transcripts involved in glial reactivity, immunometabolism and proteostasis, as well as nearly half of all Alzheimer's disease risk genes, displayed circadian oscillations, many of which were altered by pathology. Microglial oxidative stress and amyloid phagocytosis showed temporal variation in gene expression and function. Thus, circadian rhythms in gene expression are cell-dependent and context dependent, and provide important insights into glial function in health, Alzheimer's disease and aging.
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Details
- Title
- A glial circadian gene expression atlas reveals cell-type and disease-specific reprogramming in response to amyloid pathology or aging
- Creators
- Patrick W. Sheehan - Washington University in St. LouisStuart B. Fass - Washington University in St. LouisDarshan Sapkota - The University of Texas at DallasSylvia Kang - Mayo Clinic in FloridaHenry C. Hollis - Drexel UniversityJennifer H. Lawrence - Washington University in St. LouisSohui Park - Washington University in St. LouisAshish Sharma - Washington University in St. LouisDorothy P. Schafer - University of Massachusetts Chan Medical SchoolRon C. Anafi - University of PennsylvaniaJoseph D. Dougherty - Washington University in St. LouisJohn D. Fryer - Translational Genomics Research InstituteErik S. Musiek (Corresponding Author) - Washington University in St. Louis
- Publication Details
- Nature neuroscience, v 28(11), pp 2366-2379
- Publisher
- Nature Publishing
- Number of pages
- 14
- Grant note
- R00AG061231 / NINDS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) NCI Cancer Center Support Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Flow Cytometry Core at the Hope Center Alafi Neuroimaging Lab at Washington University School of Medicine T32AG058518 / U.S. Department of Health AMP; Human Services | National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; Office of the Administrator (NIH) NIH Roadmap for Medical Research; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30 CA91842 / Rockford Draper Early-Career Faculty Development Award R01NS102272 / NIA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001598734500001
- Scopus ID
- 2-s2.0-105019692314
- Other Identifier
- 991022195560704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences