Transcriptional profiling in microglia across physiological and pathological states identifies a transcriptional module associated with neurodegeneration

• Published in: Communications biology Vol. 7; no. 1; pp. 1168 - 11
• Main Authors: Guvenek, Aysegul, Parikshak, Neelroop, Zamolodchikov, Daria, Gelfman, Sahar, Moscati, Arden, Dobbyn, Lee, Stahl, Eli, Shuldiner, Alan, Coppola, Giovanni
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.09.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 38/43; 38/91; 631/114/2401; 631/378/2596/1953; 692/617/375/365; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Biomedical and Life Sciences; Central nervous system; Disease; Gene expression; Gene Expression Profiling; Gene Regulatory Networks; Genes; Genetic analysis; Genomics; Homeostasis; Humans; Life Sciences; Microglia; Microglia - metabolism; Microglia - pathology; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis - metabolism; Multiple Sclerosis - pathology; Neurodegeneration; Neurodegenerative diseases; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neuroimaging; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Physiology; Single-Cell Analysis; Transcription; Transcriptome
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06684-7

Microglia are the resident immune cells of the central nervous system and are involved in brain development, homeostasis, and disease. New imaging and genomics technologies are revealing microglial complexity across developmental and functional states, brain regions, and diseases. We curated a set of publicly available gene expression datasets from human microglia spanning disease and health to identify sets of genes reflecting physiological and pathological microglial states. We also integrated multiple human microglial single-cell RNA-seq datasets in Alzheimer’s disease (AD), multiple sclerosis (MS), and Parkinson’s disease, and identified a distinct microglial transcriptional signature shared across diseases. Analysis of germ-line DNA identified genes with variants associated with AD and MS that are overrepresented in microglial gene sets, including the disease-associated transcriptional signature. This work points to genes that are dysregulated in disease states and provides a resource for the analysis of diseases in which microglia are implicated by genetic evidence. Analysis of human microglia across health and disease identifies key gene sets in neurodegeneration, offering insights into their role in CNS disorders.