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

Laufey Geirsdottir; Eyal David; Hadas Keren-Shaul; Assaf Weiner; Stefan Cornelius Bohlen; Jana Neuber; Adam Balic; Amir Giladi; Fadi Sheban; Charles Antoine Dutertre; Christine Pfeifle; Francesca Peri; Antonella Raffo-Romero; Jacopo Vizioli; Kaspar Matiasek; Christian Scheiwe; Stephan Meckel; Kerstin Mätz-Rensing; Franziska van der Meer; Finnbogi Rutur Thormodsson; Christine Stadelmann; Noga Zilkha; Tali Kimchi; Florent Ginhoux; Igor Ulitsky; Daniel Erny; Ido Amit; Marco Prinz

doi:10.1016/j.cell.2019.11.010

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

Laufey Geirsdottir, Eyal David, Hadas Keren-Shaul, Assaf Weiner, Stefan Cornelius Bohlen, Jana Neuber, Adam Balic, Amir Giladi, Fadi Sheban, Charles Antoine Dutertre, Christine Pfeifle, Francesca Peri, Antonella Raffo-Romero, Jacopo Vizioli, Kaspar Matiasek, Christian Scheiwe, Stephan Meckel, Kerstin Mätz-Rensing, Franziska van der Meer, Finnbogi Rutur ThormodssonChristine Stadelmann, Noga Zilkha, Tali Kimchi, Florent Ginhoux, Igor Ulitsky, Daniel Erny, Ido Amit, Marco Prinz

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

264 Citations (Scopus)

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.

langue originale	Anglais
Pages (de - à)	1609-1622.e16
journal	Cell
Volume	179
Numéro de publication	7
Les DOIs	https://doi.org/10.1016/j.cell.2019.11.010
état	Publié - 12 déc. 2019
Modification externe	Oui

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10.1016/j.cell.2019.11.010

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Geirsdottir, L., David, E., Keren-Shaul, H., Weiner, A., Bohlen, S. C., Neuber, J., Balic, A., Giladi, A., Sheban, F., Dutertre, C. A., Pfeifle, C., Peri, F., Raffo-Romero, A., Vizioli, J., Matiasek, K., Scheiwe, C., Meckel, S., Mätz-Rensing, K., van der Meer, F., ... Prinz, M. (2019). Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program. Cell, 179(7), 1609-1622.e16. https://doi.org/10.1016/j.cell.2019.11.010

@article{2fcfc89ea8e94a1287e6dd96556a5327,

title = "Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program",

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",

author = "Laufey Geirsdottir and Eyal David and Hadas Keren-Shaul and Assaf Weiner and Bohlen, {Stefan Cornelius} and Jana Neuber and Adam Balic and Amir Giladi and Fadi Sheban and Dutertre, {Charles Antoine} and Christine Pfeifle and Francesca Peri and Antonella Raffo-Romero and Jacopo Vizioli and Kaspar Matiasek and Christian Scheiwe and Stephan Meckel and Kerstin M{\"a}tz-Rensing and {van der Meer}, Franziska and Thormodsson, {Finnbogi Rutur} and Christine Stadelmann and Noga Zilkha and Tali Kimchi and Florent Ginhoux and Igor Ulitsky and Daniel Erny and Ido Amit and Marco Prinz",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = dec,

day = "12",

doi = "10.1016/j.cell.2019.11.010",

language = "English",

volume = "179",

pages = "1609--1622.e16",

journal = "Cell",

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Geirsdottir, L, David, E, Keren-Shaul, H, Weiner, A, Bohlen, SC, Neuber, J, Balic, A, Giladi, A, Sheban, F, Dutertre, CA, Pfeifle, C, Peri, F, Raffo-Romero, A, Vizioli, J, Matiasek, K, Scheiwe, C, Meckel, S, Mätz-Rensing, K, van der Meer, F, Thormodsson, FR, Stadelmann, C, Zilkha, N, Kimchi, T, Ginhoux, F, Ulitsky, I, Erny, D, Amit, I & Prinz, M 2019, 'Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program', Cell, VOL. 179, Numéro 7, p. 1609-1622.e16. https://doi.org/10.1016/j.cell.2019.11.010

TY - JOUR

T1 - Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program

AU - Geirsdottir, Laufey

AU - David, Eyal

AU - Keren-Shaul, Hadas

AU - Weiner, Assaf

AU - Bohlen, Stefan Cornelius

AU - Neuber, Jana

AU - Balic, Adam

AU - Giladi, Amir

AU - Sheban, Fadi

AU - Dutertre, Charles Antoine

AU - Pfeifle, Christine

AU - Peri, Francesca

AU - Raffo-Romero, Antonella

AU - Vizioli, Jacopo

AU - Matiasek, Kaspar

AU - Scheiwe, Christian

AU - Meckel, Stephan

AU - Mätz-Rensing, Kerstin

AU - van der Meer, Franziska

AU - Thormodsson, Finnbogi Rutur

AU - Stadelmann, Christine

AU - Zilkha, Noga

AU - Kimchi, Tali

AU - Ginhoux, Florent

AU - Ulitsky, Igor

AU - Erny, Daniel

AU - Amit, Ido

AU - Prinz, Marco

PY - 2019/12/12

Y1 - 2019/12/12

N2 - 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.

AB - 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.

KW - immunology

KW - microglia

KW - neurodegeneration

KW - single-cell RNA-seq

KW - systems biology

UR - http://www.scopus.com/inward/record.url?scp=85076135131&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2019.11.010

DO - 10.1016/j.cell.2019.11.010

M3 - Article

C2 - 31835035

AN - SCOPUS:85076135131

SN - 0092-8674

VL - 179

SP - 1609-1622.e16

JO - Cell

JF - Cell

IS - 7

ER -