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 - Maetz-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
N1 - We thank Prof. Amos Tanay for important input regarding data analysis and Prof. Claudia Kemper for valuable discussion. We thank Prof. Gil Levkowitz for sharing zebrafish, and Qiyu Chen and Dr. Ludmilla Gordon for valuable technical assistance. We thank Genia Brodsky for artwork and Dr. Bjort Katrinardottir-Kragesteen, Gur Lubin, and Dr. Aleksandra Deszkowska for critical reading of the manuscript. I.A. is an Eden and Steven Romick Professorial Chair, supported by the Chan Zuckerberg Initiative (CZI), an HHMI international scholar award, a European Research Council consolidator grant (ERC-COG 724471-HemTree2.0), an MRA established investigator award (509044), DFG (SFB/TRR167), the Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine, Helen and Martin Kimmel awards for innovative investigation, an SCA award of the Wolfson Foundation and Family Charitable Trust, the Thompson Family Foundation Alzheimer’s Research Fund, the Adelis Foundation, the Eden and Steven Romick Post-Doctoral Fellowship Fund, and the International Progressive MS Alliance (PA-1604-08459). D.E. is supported by the DFG (SFB/TRR167) and the Berta Ottenstein Programme for Clinician Scientists. M.P. is supported by the Sobek Foundation, the Ernst-Jung Foundation, the DFG (SFB 992, SFB1160, SFB/TRR167, and a Reinhart Koselleck grant), and the Ministry of Science, Research and Arts, Baden-Wuerttemberg (Sonderlinie “Neuroinflammation”). This study was supported by the DFG under Germany’s Excellence Strategy (CIBSS, EXC-2189, Project ID 390939984). T.K. is supported by the ISF (grant 1324/15) and the Minerva Foundation and supervised the BMR part of the study. A.B. was supported by the Biotechnology and Biological Sciences Research Council of the United Kingdom through grants from the Institute Strategic Programme (BBS/E/D/10002071). F.G is an EMBO YIP awardee and is supported by Singapore Immunology Network (SIgN) core funding as well as a Singapore National Research Foundation senior investigatorship (NRFI; NRF2016NRF-NRFI001-02). Raw and processed single-cell and bulk RNA sequencing data will be downloaded from NCBI (GEO: GSE134707). Author Contributions Conceptualization, L.G., D.E., H.K.-S., M.P., and I.A.; Methodology, L.G., D.E., H.K.-S., A.W., and E.D.; Investigation, L.G., D.E., and H.K.-S.; Validation, L.G., D.E., H.K.-S., A.W., S.C.B., J.N., F.S., N.Z., and A.R.-R.; Genomic Data Analysis, E.D., A.W., I.U., L.G.; Image Data Analysis, D.E., M.P., and I.A.; Resources, I.A., M.P., F.G., T.K., C. Stadelmann, F.R.T., C. Scheiwe, K.M., J.V., F.P., C.P., C.A.-D., and A.B.; Data Curation, E.D.; Writing – Original Draft; L.G. and I.A.; Writing – Reviewing & Editing, I.A., H.K.-S., A.W., and L.G.; Visualization, L.G., D.E., E.D., and H.K.-S.; Supervision, M.P.; Figures 1, S1, and S4, I.A.; Figures 2, 3, 4, 5, S2, S3, S5, and S6 and Funding Acquisition: M.P. and I.A.
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.
UR - http://www.scopus.com/inward/record.url?scp=85076135131&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cell.2019.11.010
DO - https://doi.org/10.1016/j.cell.2019.11.010
M3 - مقالة
SN - 0092-8674
VL - 179
SP - 1609-1622.e16
JO - Cell
JF - Cell
IS - 7
ER -