TY - JOUR T1 - Transcriptional landscape of human microglia reveals robust gene expression signatures that implicates age, sex and <em>APOE</em>-related immunometabolic pathway perturbations JF - bioRxiv DO - 10.1101/2021.05.13.444000 SP - 2021.05.13.444000 AU - Tulsi Patel AU - Troy P. Carnwath AU - Xue Wang AU - Mariet Allen AU - Sarah J. Lincoln AU - Laura J. Lewis-Tuffin AU - Zachary S. Quicksall AU - Shu Lin AU - Frederick Q. Tutor-New AU - Charlotte C.G. Ho AU - Yuhao Min AU - Kimberly G. Malphrus AU - Thuy T. Nguyen AU - Elizabeth Martin AU - Cesar A. Garcia AU - Rawan M. Alkharboosh AU - Sanjeet Grewal AU - Kaisorn Chaichana AU - Robert Wharen AU - Hugo Guerrero-Cazares AU - Alfredo Quinones-Hinojosa AU - Nilüfer Ertekin-Taner Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/16/2021.05.13.444000.abstract 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 data from 1,306 brain samples across 6 regions and in single cell microglia transcriptome. 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. 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.Competing Interest StatementThe authors have declared no competing interest.ADAlzheimer’s diseaseAPOEApolipoproteinEBMBrodmann’s areaBSABovine serum albuminCERADConsortium to Establish a Registry for Alzheimer’s DiseaseCNSCentral nervous systemCQNConditional quantile normalizationDAMDisease-associated microgliaDPBSDulbecco’s phosphate buffered salineFACSFluorescence-activated cell sortingFPKMFragments per kilobase of transcript per million mapped readsGEMGel bead-in emulsionGOGene ontologyMACSMagnetic-activated cell sortingMEModule eigengenesMMModule membershipPBSPhosphate buffered salinePCPrincipal componentPCAPrinciple component analysisPFAParaformaldehydeQCQuality controlRNAseqRNA sequencingROSMAPRush University Religious Order Study-Memory and Aging ProjectscRNAseqSingle cell RNA sequencingsnRNAseqSingle nuclei RNA sequencingUMIUnique molecular identifierWGCNAWeighted gene co-expression network analysis ER -