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Cell. 2019 Dec 12;179(7):1609-1622.e16. doi: 10.1016/j.cell.2019.11.010.

Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program.

Author information

1
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
2
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; Life Science Core Facility-Israel National Center for Personalized Medicine (G-INCPM), Weizmann Institute of Science, Rehovot, Israel.
3
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
4
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, EH25 9RG, United Kingdom.
5
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore; Program in Emerging Infectious Disease, Duke-NUS Medical School, 8 College Road, Singapore, Singapore.
6
Department of Evolutionary Genetics, Max-Planck-Institute for Evolutionary Biology, Ploen, Germany.
7
Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
8
Universite Lille, Inserm, U-1192-Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, Lille, France.
9
Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
10
Clinic for Neurosurgery, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
11
Department of Neuroradiology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
12
German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany.
13
Innovation Center Iceland, Reykjavik, Iceland.
14
Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
15
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
16
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore; Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China; Translational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, the Academia, Singapore, Singapore.
17
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
18
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: daniel.erny@uniklinik-freiburg.de.
19
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: ido.amit@weizmann.ac.il.
20
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Signaling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany; Center for NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: marco.prinz@uniklinik-freiburg.de.

Abstract

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.

KEYWORDS:

immunology; microglia; neurodegeneration; single-cell RNA-seq; systems biology

PMID:
31835035
DOI:
10.1016/j.cell.2019.11.010

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