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

Tulsi Patel, Troy P. Carnwath, Xue Wang, Mariet Allen, Sarah J. Lincoln, Laura J Lewis-Tuffin, Zachary S. Quicksall, Shu Lin, Frederick Q. Tutor-New, Charlotte C.G. Ho, Yuhao Min, Kimberly G. Malphrus, Thuy T. Nguyen, Elizabeth Martin, Cesar A. Garcia, Rawan M. Alkharboosh, Sanjeet Grewal, Kaisorn Chaichana, Robert E Wharen, Jr, Hugo Guerrero-CazaresAlfredo Quinones-Hinojosa, Nilüfer Ertekin-Taner

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalAging Cell
DOIs
StateAccepted/In press - 2022

Keywords

  • APOE
  • lipid metabolism
  • microglia
  • neurodegeneration
  • single cell
  • transcriptomics

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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