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


Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
12 12 2019
Historique:
received: 12 03 2019
revised: 30 07 2019
accepted: 06 11 2019
entrez: 14 12 2019
pubmed: 14 12 2019
medline: 6 6 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31835035
pii: S0092-8674(19)31231-0
doi: 10.1016/j.cell.2019.11.010
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1609-1622.e16

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/D/20320000
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Laufey Geirsdottir (L)

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

Eyal David (E)

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

Hadas Keren-Shaul (H)

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.

Assaf Weiner (A)

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

Stefan Cornelius Bohlen (SC)

Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Jana Neuber (J)

Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Adam Balic (A)

The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, EH25 9RG, United Kingdom.

Amir Giladi (A)

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

Fadi Sheban (F)

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

Charles-Antoine Dutertre (CA)

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.

Christine Pfeifle (C)

Department of Evolutionary Genetics, Max-Planck-Institute for Evolutionary Biology, Ploen, Germany.

Francesca Peri (F)

Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

Antonella Raffo-Romero (A)

Universite Lille, Inserm, U-1192-Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, Lille, France.

Jacopo Vizioli (J)

Universite Lille, Inserm, U-1192-Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, Lille, France.

Kaspar Matiasek (K)

Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.

Christian Scheiwe (C)

Clinic for Neurosurgery, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Stephan Meckel (S)

Department of Neuroradiology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Kerstin Mätz-Rensing (K)

German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany.

Franziska van der Meer (F)

German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany.

Finnbogi Rutur Thormodsson (FR)

Innovation Center Iceland, Reykjavik, Iceland.

Christine Stadelmann (C)

Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.

Noga Zilkha (N)

Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.

Tali Kimchi (T)

Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.

Florent Ginhoux (F)

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.

Igor Ulitsky (I)

Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.

Daniel Erny (D)

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.

Ido Amit (I)

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: ido.amit@weizmann.ac.il.

Marco Prinz (M)

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.

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