المؤلفون: Ydens, Elke, Amann, Lukas, Asselbergh, Bob, Scott, Charlotte L., Martens, Liesbet, Sichien, Dorine, Mossad, Omar, Blank, Thomas, De Prijck, Sofie, Low, Donovan, Masuda, Takahiro, Saeys, Yvan, Timmerman, Vincent, Stumm, Ralf, Ginhoux, Florent, Prinz, Marco, Janssens, Sophie, Guilliams, Martin

المصدر: Nature Neuroscience; May 2020, Vol. 23 Issue: 5 p676-689, 14p

مستخلص: While CNS microglia have been extensively studied, relatively little is known about macrophages populating the peripheral nervous system. Here we performed ontogenic, transcriptomic and spatial characterization of sciatic nerve macrophages (snMacs). Using multiple fate-mapping systems, we show that snMacs do not derive from the early embryonic precursors colonizing the CNS, but originate primarily from late embryonic precursors and become replaced by bone-marrow-derived macrophages over time. Using single-cell transcriptomics, we identified a tissue-specific core signature of snMacs and two spatially separated snMacs: Relmα+Mgl1+snMacs in the epineurium and Relmα–Mgl1–snMacs in the endoneurium. Globally, snMacs lack most of the core signature genes of microglia, with only the endoneurial subset expressing a restricted number of these genes. In response to nerve injury, the two resident snMac populations respond differently. Moreover, and unlike in the CNS, monocyte-derived macrophages that develop during injury can engraft efficiently in the pool of resident peripheral nervous system macrophages.

المؤلفون: Van Hove, Hannah, Martens, Liesbet, Scheyltjens, Isabelle, De Vlaminck, Karen, Pombo Antunes, Ana Rita, De Prijck, Sofie, Vandamme, Niels, De Schepper, Sebastiaan, Van Isterdael, Gert, Scott, Charlotte L., Aerts, Jeroen, Berx, Geert, Boeckxstaens, Guy E., Vandenbroucke, Roosmarijn E., Vereecke, Lars, Moechars, Diederik, Guilliams, Martin, Van Ginderachter, Jo A., Saeys, Yvan, Movahedi, Kiavash

المصدر: Nature Neuroscience; June 2019, Vol. 22 Issue: 6 p1021-1035, 15p

مستخلص: While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less well understood. By dissecting border regions and combining single-cell RNA-sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny, and subsets displayed distinct self-renewal capacity following depletion and repopulation. Single-cell and fate-mapping analysis both suggested that there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host–macrophage interactions in both the healthy and diseased brain.

المؤلفون: Scott, Charlotte E^1,2, Wynn, Sarah L^1,3, Sesay, Abdul¹, Cruz, Catarina², Cheung, Martin^2,3, Gaviro, Maria-Victoria Gomez¹, Booth, Sarah¹, Bo Gao³, Cheah, Kathryn S. E.³, Lovell-Badge, Robin¹ rlovell@nimr.mrc.ac.uk, Briscoe, James² jbrisco@nimr.mrc.ac.uk

المصدر: Nature Neuroscience. Oct2010, Vol. 13 Issue 10, p1181-1189. 9p. 4 Color Photographs, 1 Black and White Photograph, 3 Graphs.

مصطلحات موضوعية: *NEURAL stem cells, *CENTRAL nervous system, *LABORATORY mice, *GENE expression, *NEUROLOGY

مستخلص: Neural stem cells (NSCs) are uncommitted cells of the CNS defined by their multipotentiality and ability to self renew. We found these cells to not be present in substantial numbers in the CNS until after embryonic day (E) 10.5 in mouse and E5 in chick. This coincides with the induction of SOX9 in neural cells. Gain- and loss-of-function studies indicated that SOX9 was essential for multipotent NSC formation. Moreover, Sonic Hedgehog was able to stimulate precocious generation of NSCs by inducing Sox9 expression. SOX9 was also necessary for the maintenance of multipotent NSCs, as shown by in vivo fate mapping experiments in the adult subependymal zone and olfactory bulbs. In addition, loss of SOX9 led ependymal cells to adopt a neuroblast identity. These data identify a functional link between extrinsic and intrinsic mechanisms of NSCs specification and maintenance, and establish a central role for SOX9 in the process. [ABSTRACT FROM AUTHOR]