A map of transcriptional heterogeneity and regulatory variation in human microglia.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
15
05
2020
accepted:
23
04
2021
pubmed:
5
6
2021
medline:
21
7
2021
entrez:
4
6
2021
Statut:
ppublish
Résumé
Microglia, the tissue-resident macrophages of the central nervous system (CNS), play critical roles in immune defense, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single-cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using a human induced pluripotent stem cell-based macrophage model to fine-map a candidate causal variant for Alzheimer's disease at the BIN1 locus. Our study provides a population-scale transcriptional map of a critically important cell for human CNS development and disease.
Identifiants
pubmed: 34083789
doi: 10.1038/s41588-021-00875-2
pii: 10.1038/s41588-021-00875-2
pmc: PMC7610960
mid: EMS123217
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
861-868Subventions
Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : Wellcome Trust
ID : RRZD/029
Pays : United Kingdom
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : Wellcome Trust
ID : 206194
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203151
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
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