Journal ArticleDOI
Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways
Katrin Kierdorf,Daniel Erny,Tobias Goldmann,Victor Sander,Christian Schulz,Elisa Gomez Perdiguero,Peter Wieghofer,Annette Heinrich,Pia Riemke,Christoph Hölscher,Dominik N. Müller,Bruno Luckow,Thomas Brocker,Katharina Debowski,Günter Fritz,Ghislain Opdenakker,Andreas Diefenbach,Knut Biber,Knut Biber,Mathias Heikenwalder,Frederic Geissmann,Frank Rosenbauer,Marco Prinz +22 more
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TLDR
It is found that mouse microglia were derived from primitive c-kit+ erythromyeloid precursors that were detected in the yolk sac as early as 8 d post conception and microgliogenesis was not only dependent on the transcription factor Pu.1, but also required Irf8, which was vital for the development of the A2 population, whereas Myb, Id2, Batf3 and Klf4 were not required.Abstract:
Microglia are crucial for immune responses in the brain. Although their origin from the yolk sac has been recognized for some time, their precise precursors and the transcription program that is used are not known. We found that mouse microglia were derived from primitive c-kit(+) erythromyeloid precursors that were detected in the yolk sac as early as 8 d post conception. These precursors developed into CD45(+) c-kit(lo) CX(3)CR1(-) immature (A1) cells and matured into CD45(+) c-kit(-) CX(3)CR1(+) (A2) cells, as evidenced by the downregulation of CD31 and concomitant upregulation of F4/80 and macrophage colony stimulating factor receptor (MCSF-R). Proliferating A2 cells became microglia and invaded the developing brain using specific matrix metalloproteinases. Notably, microgliogenesis was not only dependent on the transcription factor Pu.1 (also known as Sfpi), but also required Irf8, which was vital for the development of the A2 population, whereas Myb, Id2, Batf3 and Klf4 were not required. Our data provide cellular and molecular insights into the origin and development of microglia.read more
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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
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Oleg Butovsky,Mark P. Jedrychowski,Craig S. Moore,Ron Cialic,Amanda J. Lanser,Galina Gabriely,Thomas Koeglsperger,Ben Dake,Pauline M. Wu,Camille Doykan,Zain Fanek,LiPing Liu,Zhuoxun Chen,Jeffrey D. Rothstein,Richard M. Ransohoff,Steven P. Gygi,Jack P. Antel,Howard L. Weiner +17 more
TL;DR: It is found that TGF-β was required for the in vitro development of microglia that express the microglial molecular signature characteristic of adultmicroglia and that microglian were absent in the CNS of TGF -β1–deficient mice.
Journal Article
A lineage of myeloid cells independent of Myb and hematopoietic stem cells
Elisa Gomez Perdiguero,Christian Schulz,Laurent Chorro,Heather L. Szabo-Rogers,Nicolas Cagnard,Katrin Kierdorf,Marco Prinz,Bishan Wu,Jacobsen Sew.,Jeffrey W. Pollard,Jon Frampton,Karen J. Liu,Frederic Geissmann +12 more
TL;DR: Schulz et al. as discussed by the authors investigated whether adult macrophages all share a common developmental origin and found that a population of yolk-sac-derived, tissue-resident macophages was able to develop and persist in adult mice in the absence of hematopoietic stem cells.
Journal ArticleDOI
Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors
Elisa Gomez Perdiguero,Kay Klapproth,Christian Schulz,Katrin Busch,Emanuele Azzoni,Lucile Crozet,Hannah Garner,Céline Trouillet,Marella F. T. R. de Bruijn,Frederic Geissmann,Hans Reimer Rodewald +10 more
TL;DR: It is shown in mice that the vast majority of adult tissue-resident macrophages originate from a Tie2+ (also known as Tek) cellular pathway generating Csf1r+ erythro-myeloid progenitors (EMPs) distinct from HSCs.
Journal ArticleDOI
Monocytes and macrophages: developmental pathways and tissue homeostasis
Florent Ginhoux,Steffen Jung +1 more
TL;DR: The evidence that has dramatically changed the authors' understanding of monocyte and macrophage development, and the maintenance of these cells in the steady state is discussed.
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
Blood Monocytes Consist of Two Principal Subsets with Distinct Migratory Properties
TL;DR: Using a murine adoptive transfer system to probe monocyte homing and differentiation in vivo, two functional subsets among murine blood monocytes are identified: a short-lived CX(3)CR1(lo)CCR2(+)Gr1(+) subset that is actively recruited to inflamed tissues and a CX (3) CR1(hi)CCS1-dependent recruitment to noninflamed tissues.
Journal ArticleDOI
Microglia: active sensor and versatile effector cells in the normal and pathologic brain
TL;DR: This review focuses on several key observations that illustrate the multi-faceted activities of microglia in the normal and pathologic brain.
Journal ArticleDOI
Development of Monocytes, Macrophages, and Dendritic Cells
TL;DR: The current understanding of myeloid lineage development is reviewed and the developmental pathways and cues that drive differentiation are described, which are central to the development of immunologic memory and tolerance in mice.
Journal ArticleDOI
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
TL;DR: The prospective identification, purification and characterization, using cell-surface markers and flow cytometry, of a complementary clonogenic common myeloid progenitor that gives rise to all myeloids lineages is reported.