Transcriptional landscape of human microglia implicates age, sex, and APOE-related immunometabolic pathway perturbations.

Autor: Patel T; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Carnwath TP; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Wang X; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida, USA., Allen M; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Lincoln SJ; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Lewis-Tuffin LJ; Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, USA., Quicksall ZS; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida, USA., Lin S; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Tutor-New FQ; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Ho CCG; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Min Y; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Malphrus KG; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Nguyen TT; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Martin E; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Garcia CA; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Alkharboosh RM; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA.; Neuroscience Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota, USA.; Regenerative Sciences Training Program, Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota, USA., Grewal S; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Chaichana K; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Wharen R; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Guerrero-Cazares H; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Quinones-Hinojosa A; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Ertekin-Taner N; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.; Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2022 May; Vol. 21 (5), pp. e13606. Date of Electronic Publication: 2022 Apr 06.
DOI: 10.1111/acel.13606
Abstrakt: Microglia have fundamental roles in health and disease; however, effects of age, sex, and genetic factors on human microglia have not been fully explored. We applied bulk and single-cell approaches to comprehensively characterize human microglia transcriptomes and their associations with age, sex, and APOE. We identified a novel microglial signature, characterized its expression in bulk tissue and single-cell microglia transcriptomes. We discovered microglial co-expression network modules associated with age, sex, and APOE-ε4 that are enriched for lipid and carbohydrate metabolism genes. Integrated analyses of modules with single-cell transcriptomes revealed significant overlap between age-associated module genes and both pro-inflammatory and disease-associated microglial clusters. These modules and clusters harbor known neurodegenerative disease genes including APOE, PLCG2, and BIN1. Meta-analyses with published bulk and single-cell microglial datasets further supported our findings. Thus, these data represent a well-characterized human microglial transcriptome resource and highlight age, sex, and APOE-related microglial immunometabolism perturbations with potential relevance in neurodegeneration.
(© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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