期刊
CELL
卷 179, 期 7, 页码 1609-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2019.11.010
关键词
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资金
- Chan Zuckerberg Initiative (CZI)
- HHMI international scholar award
- European Research Council [ERCCOG 724471-HemTree2.0]
- MRA established investigator award [509044]
- DFG [SFB 992, SFB1160, SFB/TRR167]
- Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine
- Helen and Martin Kimmel awards for innovative investigation
- SCA award of the Wolfson Foundation
- Family Charitable Trust
- Thompson Family Foundation Alzheimer's Research Fund
- Adelis Foundation
- Eden and Steven Romick PostDoctoral Fellowship Fund
- International Progressive MS Alliance [PA-1604-08459]
- Berta Ottenstein Programme for Clinician Scientists
- Sobek Foundation
- Ernst-Jung Foundation
- Ministry of Science, Research and Arts, Baden-Wuerttemberg (Sonderlinie Neuroinflammation'')
- DFG under Germany's Excellence Strategy (CIBSS) [EXC-2189, 390939984]
- ISF [1324/15]
- Minerva Foundation
- Biotechnology and Biological Sciences Research Council of the United Kingdom through Institute Strategic Programme [BBS/E/D/10002071]
- Singapore Immunology Network (SIgN) core funding
- Singapore National Research Foundation senior investigatorship (NRFI) [NRF2016NRF-NRFI001-02]
- DFG (Reinhart Koselleck grant)
- BBSRC [BB/R003653/1, BBS/E/D/20320000, BBS/E/D/10002071] Funding Source: UKRI
Microglia, the brain-resident immune cells, are critically involved in many physiological and pathological brain processes, including neurodegeneration. Here we characterize microglia morphology and transcriptional programs across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to humans, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, whereas human microglia display significant heterogeneity. In addition, we observed notable differences in several gene modules of rodents compared with primate microglia, including complement, phagocytic, and susceptibility genes to neurodegeneration, such as Alzheimer's and Parkinson's disease. Our study provides an essential resource of conserved and divergent microglia pathways across evolution, with important implications for future development of microglia-based therapies in humans.
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