ZFIN ID: ZDB-PUB-200606-35
Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program
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.
Date: 2019
Source: Cell   179: 1609-1622.e16 (Journal)
Registered Authors: Peri, Francesca
Keywords: immunology, microglia, neurodegeneration, single-cell RNA-seq, systems biology
Microarrays: 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
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.