Open AccessTranscriptional landscape of human microglia implicates age, sex, and APOE ‐related immunometabolic pathway perturbations
Author(s) -
Patel Tulsi,
Carnwath Troy P.,
Wang Xue,
Allen Mariet,
Lincoln Sarah J.,
LewisTuffin Laura J.,
Quicksall Zachary S.,
Lin Shu,
TutorNew Frederick Q.,
Ho Charlotte C.G.,
Min Yuhao,
Malphrus Kimberly G.,
Nguyen Thuy T.,
Martin Elizabeth,
Garcia Cesar A.,
Alkharboosh Rawan M.,
Grewal Sanjeet,
Chaichana Kaisorn,
Wharen Robert,
GuerreroCazares Hugo,
QuisHinojosa Alfredo,
ErtekinTaner Nilüfer
Publication year - 2022
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13606
Subject(s) - microglia , transcriptome , biology , apolipoprotein e , neurodegeneration , gene , disease , computational biology , gene expression , genetics , immunology , inflammation , medicine
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.