PUBLICATION

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

Authors
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., Thormodsson, F.R., Stadelmann, C., Zilkha, N., Kimchi, T., Ginhoux, F., Ulitsky, I., Erny, D., Amit, I., Prinz, M.
ID
ZDB-PUB-200606-35
Date
2019
Source
Cell   179: 1609-1622.e16 (Journal)
Registered Authors
Peri, Francesca
Keywords
immunology, microglia, neurodegeneration, single-cell RNA-seq, systems biology
Datasets
GEO:GSE134705, GEO:GSE134706, GEO:GSE134707
MeSH Terms
  • Animals
  • Chickens
  • Evolution, Molecular*
  • Gene Expression Profiling
  • Gene Regulatory Networks*
  • Genetic Predisposition to Disease
  • Humans
  • Microglia/metabolism*
  • Neurodegenerative Diseases/genetics*
  • Primates
  • Reptiles
  • Rodentia
  • Sheep
  • Single-Cell Analysis*
  • Swine
  • Transcriptome*
  • Zebrafish
PubMed
31835035 Full text @ Cell
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes
This article is corrected by ZDB-PUB-220906-202 .