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

ABSTRACT: 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.

SUBMITTER: Patel T

PROVIDER: S-EPMC9124307 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Patel Tulsi T Carnwath Troy P TP Wang Xue X Allen Mariet M Lincoln Sarah J SJ Lewis-Tuffin Laura J LJ Quicksall Zachary S ZS Lin Shu S Tutor-New Frederick Q FQ Ho Charlotte C G CCG Min Yuhao Y Malphrus Kimberly G KG Nguyen Thuy T TT Martin Elizabeth E Garcia Cesar A CA Alkharboosh Rawan M RM Grewal Sanjeet S Chaichana Kaisorn K Wharen Robert R Guerrero-Cazares Hugo H Quinones-Hinojosa Alfredo A Ertekin-Taner Nilüfer N

Aging cell 20220406 5

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 associ ...[more]

PMID: 35388616

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Dataset Information

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

Publications

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

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