PT  - JOURNAL ARTICLE
AU  - Katherine E. Prater
AU  - Kevin J. Green
AU  - Sainath Mamde
AU  - Wei Sun
AU  - Alexandra Cochoit
AU  - Carole L. Smith
AU  - Kenneth L. Chiou
AU  - Laura Heath
AU  - Shannon E. Rose
AU  - Jesse Wiley
AU  - C. Dirk Keene
AU  - Ronald Y. Kwon
AU  - Noah Snyder-Mackler
AU  - Elizabeth E. Blue
AU  - Benjamin Logsdon
AU  - Jessica E. Young
AU  - Ali Shojaie
AU  - Gwenn A. Garden
AU  - Suman Jayadev
TI  - Transcriptomically unique endolysosomal and homeostatic microglia populations in Alzheimer’s disease and aged human brain
AID  - 10.1101/2021.10.25.465802
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2021.10.25.465802
4099  - http://biorxiv.org/content/early/2022/11/18/2021.10.25.465802.short
4100  - http://biorxiv.org/content/early/2022/11/18/2021.10.25.465802.full
AB  - Microglia contribute to Alzheimer’s Disease (AD) progression and are candidate therapeutic targets. Human microglia exhibit an array of transcriptional phenotypes implying that accurate manipulation of microglial function will require clarity of their molecular states and context dependent regulation. To increase the number of microglia analyzed per subject we employed fluorescence activated nuclei sorting prior to single-nucleus RNA-seq on human prefrontal cortices. We observed microglia phenotypes previously unrecognized in human brain gene expression studies and mapped their transcriptomic relationships by trajectory inference. Three clusters were enriched for endolysosomal pathways, one of which showed differential expression of AD GWAS genes in addition to genes implicated in nucleic acid detection and interferon signaling. Analysis of the “homeostatic” microglia cluster revealed a uniquely AD subcluster. Our study demonstrates the value of deeply profiling microglia to explore the biological implications of microglia transcriptomic diversity.Competing Interest StatementThe authors have declared no competing interest.