Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program
- PMID: 31835035
- DOI: 10.1016/j.cell.2019.11.010
Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program
Erratum in
-
Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program.Cell. 2020 Apr 30;181(3):746. doi: 10.1016/j.cell.2020.04.002. Cell. 2020. PMID: 32359440 No abstract available.
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.
Copyright © 2019 Elsevier Inc. All rights reserved.
Similar articles
-
Transcriptional profiling in microglia across physiological and pathological states identifies a transcriptional module associated with neurodegeneration.Commun Biol. 2024 Sep 18;7(1):1168. doi: 10.1038/s42003-024-06684-7. Commun Biol. 2024. PMID: 39294270 Free PMC article.
-
Genome-wide RNAseq study of the molecular mechanisms underlying microglia activation in response to pathological tau perturbation in the rTg4510 tau transgenic animal model.Mol Neurodegener. 2018 Dec 17;13(1):65. doi: 10.1186/s13024-018-0296-y. Mol Neurodegener. 2018. PMID: 30558641 Free PMC article.
-
A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease.Cell. 2017 Jun 15;169(7):1276-1290.e17. doi: 10.1016/j.cell.2017.05.018. Epub 2017 Jun 8. Cell. 2017. PMID: 28602351
-
Transcriptional Networks of Microglia in Alzheimer's Disease and Insights into Pathogenesis.Genes (Basel). 2019 Oct 12;10(10):798. doi: 10.3390/genes10100798. Genes (Basel). 2019. PMID: 31614849 Free PMC article. Review.
-
Microglia heterogeneity and neurodegeneration: The emerging paradigm of the role of immunity in Alzheimer's disease.J Neuroimmunol. 2020 Apr 15;341:577185. doi: 10.1016/j.jneuroim.2020.577185. Epub 2020 Feb 3. J Neuroimmunol. 2020. PMID: 32045774 Review.
Cited by
-
MET receptor serves as a promising target in melanoma brain metastases.Acta Neuropathol. 2024 Feb 22;147(1):44. doi: 10.1007/s00401-024-02694-1. Acta Neuropathol. 2024. PMID: 38386085 Free PMC article.
-
Hypothalamic Microglial Heterogeneity and Signature under High Fat Diet-Induced Inflammation.Int J Mol Sci. 2021 Feb 24;22(5):2256. doi: 10.3390/ijms22052256. Int J Mol Sci. 2021. PMID: 33668314 Free PMC article. Review.
-
Single-cell and single-nuclei RNA sequencing as powerful tools to decipher cellular heterogeneity and dysregulation in neurodegenerative diseases.Front Cell Dev Biol. 2022 Oct 24;10:884748. doi: 10.3389/fcell.2022.884748. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 36353512 Free PMC article. Review.
-
Validation of Induced Microglia-Like Cells (iMG Cells) for Future Studies of Brain Diseases.Front Cell Neurosci. 2021 Apr 9;15:629279. doi: 10.3389/fncel.2021.629279. eCollection 2021. Front Cell Neurosci. 2021. PMID: 33897370 Free PMC article.
-
Human neuronal maturation comes of age: cellular mechanisms and species differences.Nat Rev Neurosci. 2024 Jan;25(1):7-29. doi: 10.1038/s41583-023-00760-3. Epub 2023 Nov 23. Nat Rev Neurosci. 2024. PMID: 37996703 Review.
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases