Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation
Top Cited Papers
- 25 January 2019
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 363 (6425), 365-+
- https://doi.org/10.1126/science.aat7554
Abstract
The innate immune cell compartment is highly diverse in the healthy central nervous system (CNS), including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are. Combining deep single-cell transcriptome analysis, fate mapping, in vivo imaging, clonal analysis, and transgenic mouse lines, we comprehensively characterized unappreciated myeloid subsets in several CNS compartments during neuroinflammation. During inflammation, CNS macrophage subsets undergo self-renewal, and random proliferation shifts toward clonal expansion. Last, functional studies demonstrated that endogenous CNS tissue macrophages are redundant for antigen presentation. Our results highlight myeloid cell diversity and provide insights into the brain’s innate immune system.This publication has 72 references indexed in Scilit:
- Microglial nodules in early multiple sclerosis white matter are associated with degenerating axonsActa Neuropathologica, 2013
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- The role of antigen presenting cells in multiple sclerosisBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2011
- Fast and accurate long-read alignment with Burrows–Wheeler transformBioinformatics, 2010
- CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous systemBrain, 2009
- Fast and accurate short read alignment with Burrows–Wheeler transformBioinformatics, 2009
- Localizing central nervous system immune surveillance: Meningeal antigen‐presenting cells activate T cells during experimental autoimmune encephalomyelitisAnnals of Neurology, 2009
- Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating diseaseBlood, 2009
- Debris clearance by microglia: an essential link between degeneration and regenerationBrain, 2008
- Multiple sclerosis: a complicated picture of autoimmunityNature Immunology, 2007