TY - JOUR
T1 - Transcriptional landscape of human microglia implicates age, sex, and APOE-related immunometabolic pathway perturbations
AU - Patel, Tulsi
AU - Carnwath, Troy P.
AU - Wang, Xue
AU - Allen, Mariet
AU - Lincoln, Sarah J.
AU - Lewis-Tuffin, Laura J
AU - Quicksall, Zachary S.
AU - Lin, Shu
AU - Tutor-New, Frederick Q.
AU - Ho, Charlotte C.G.
AU - Min, Yuhao
AU - Malphrus, Kimberly G.
AU - Nguyen, Thuy T.
AU - Martin, Elizabeth
AU - Garcia, Cesar A.
AU - Alkharboosh, Rawan M.
AU - Grewal, Sanjeet
AU - Chaichana, Kaisorn
AU - Wharen, Robert
AU - Guerrero-Cazares, Hugo
AU - Quinones-Hinojosa, Alfredo
AU - Ertekin-Taner, Nilüfer
N1 - Publisher Copyright:
© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - APOE
KW - lipid metabolism
KW - microglia
KW - neurodegeneration
KW - single cell
KW - transcriptomics
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U2 - 10.1111/acel.13606
DO - 10.1111/acel.13606
M3 - Article
C2 - 35388616
AN - SCOPUS:85127537913
SN - 1474-9718
VL - 21
JO - Aging Cell
JF - Aging Cell
IS - 5
M1 - e13606
ER -