Journal ArticleDOI
Ontogeny and homeostasis of CNS myeloid cells.
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TLDR
Studies using cell-specific targeting, in vivo imaging, single-cell expression analysis and other sophisticated tools have increased the depth of knowledge of this immune-cell compartment and call for reevaluation of the traditional views on the origin, fate and function of distinct CNS myeloid subsets.Abstract:
Myeloid cells in the central nervous system (CNS) represent a heterogeneous class of innate immune cells that contribute to the maintenance of tissue homeostasis differentially during development and adulthood. The subsets of CNS myeloid cells identified so far, including parenchymal microglia and non-parenchymal meningeal, perivascular and choroid-plexus macrophages, as well as disease-associated monocytes, have classically been distinguished on the basis of their surface epitope expression, localization and morphology. However, studies using cell-specific targeting, in vivo imaging, single-cell expression analysis and other sophisticated tools have now increased the depth of knowledge of this immune-cell compartment and call for reevaluation of the traditional views on the origin, fate and function of distinct CNS myeloid subsets. The concepts of CNS macrophage biology that are emerging from these new insights have broad implications for the understanding and treatment of CNS diseases.read more
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Microglia in Central Nervous System Inflammation and Multiple Sclerosis Pathology.
TL;DR: This work has shown that microglia respond to changes in the microenvironment, and the resulting reactive phenotype can be very diverse, with both neuroinflammatory and neuroprotective properties, illustrating the plasticity of these cells.
Journal ArticleDOI
Mapping microglia states in the human brain through the integration of high-dimensional techniques
Roman Sankowski,Chotima Böttcher,Takahiro Masuda,Laufey Geirsdottir,Sagar,Elena Sindram,Tamara Seredenina,Andreas Muhs,Christian Scheiwe,Mukesch Shah,Dieter Henrik Heiland,Oliver Schnell,Dominic Grün,Dominic Grün,Josef Priller,Josef Priller,Marco Prinz +16 more
TL;DR: Two high-dimensional technologies are combined, single-cell RNA-sequencing and time-of-flight mass cytometry, to identify and characterize a previously unappreciated spectrum of transcriptional states in human microglia, identifying a spectrum of microglian phenotypes that are determined by localization, aging and glioblastoma.
Journal ArticleDOI
Myeloid Cells in the Central Nervous System.
TL;DR: The neuroprotective nature of certain myeloid cells are highlighted by emphasizing their therapeutic potential for the treatment of neurological conditions and the role of these cells in various neurological pathologies, such as autoimmunity, mechanical injury, neurodegeneration, and infection are discussed.
Journal ArticleDOI
Macrophages at CNS interfaces: ontogeny and function in health and disease.
TL;DR: Several specialized macrophage populations reside in the structures that border the mammalian CNS, including the meninges, perivascular spaces and choroid plexus, and are reviewed to suggest central roles for CAMs in CNS physiology and in the pathogenesis of diseases.
Posted ContentDOI
Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing
Qingyun Li,Zuolin Cheng,Lu Zhou,Spyros Darmanis,Norma F. Neff,Jennifer Okamoto,Gunsagar S. Gulati,Mariko L. Bennett,Lu O. Sun,Laura E. Clarke,Julia Marschallinger,Guoqiang Yu,Stephen R. Quake,Tony Wyss-Coray,Ben A. Barres +14 more
TL;DR: Deep single-cell RNA sequencing of microglia and related myeloid cells sorted from various regions of embryonic, postnatal, and adult mouse brains found that the majority of adult microglian signatures are remarkably similar in transcriptomes, regardless of brain region.
References
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Journal ArticleDOI
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Florent Ginhoux,Florent Ginhoux,Melanie Greter,Marylene Leboeuf,Sayan Nandi,Peter See,Solen Gokhan,Mark F. Mehler,Simon J. Conway,Lai Guan Ng,E. Richard Stanley,Igor M. Samokhvalov,Miriam Merad +12 more
TL;DR: Results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.
Journal ArticleDOI
Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
Amit Zeisel,Ana B. Muñoz-Manchado,Simone Codeluppi,Peter Lönnerberg,Gioele La Manno,Anna Juréus,Sueli Marques,Hermany Munguba,Liqun He,Christer Betsholtz,Christer Betsholtz,Charlotte Rolny,Gonçalo Castelo-Branco,Jens Hjerling-Leffler,Sten Linnarsson +14 more
TL;DR: Large-scale single-cell RNA sequencing is used to classify cells in the mouse somatosensory cortex and hippocampal CA1 region and found 47 molecularly distinct subclasses, comprising all known major cell types in the cortex.
Journal ArticleDOI
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Simon Yona,Ki-Wook Kim,Yochai Wolf,Alexander Mildner,Diana Varol,Michal Breker,Dalit Strauss-Ayali,Sergey Viukov,Martin Guilliams,Alexander V. Misharin,David A. Hume,Harris Perlman,Bernard Malissen,Elazar Zelzer,Steffen Jung +14 more
TL;DR: A fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression is reported, establishing that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly 6C(-) cells and that the abundance of Ly6 C(+) blood monocytes dynamically controls the circulation lifespan of their progeny.
Journal ArticleDOI
Host microbiota constantly control maturation and function of microglia in the CNS
Daniel Erny,Anna Lena Hrabě de Angelis,Diego Jaitin,Peter Wieghofer,Ori Staszewski,Eyal David,Hadas Keren-Shaul,Tanel Mahlakõiv,Kristin Jakobshagen,Thorsten Buch,Vera Schwierzeck,Olaf Utermöhlen,Eunyoung Chun,Wendy S. Garrett,Kathy D. McCoy,Andreas Diefenbach,Peter Staeheli,Bärbel Stecher,Ido Amit,Marco Prinz +19 more
TL;DR: It is determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis and mice deficient for the SCFA receptor FFAR2 mirroredmicroglia defects found under GF conditions, suggesting that host bacteria vitally regulate microglian maturation and function.
Journal ArticleDOI
A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells
Christian Schulz,Elisa Gomez Perdiguero,Laurent Chorro,Heather L. Szabo-Rogers,Nicolas Cagnard,Katrin Kierdorf,Marco Prinz,Bishan Wu,Sten Eirik W. Jacobsen,Jeffrey W. Pollard,Jon Frampton,Karen J. Liu,Frederic Geissmann +12 more
TL;DR: It is found that the transcription factor Myb was required for development of HSCs and all CD11bhigh monocytes and macrophages, but was dispensable for yolk sac (YS)macrophages and for the development of YS-derived F4/80bright macrophage populations in several tissues.