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A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages.
Brioschi, Simone; Belk, Julia A; Peng, Vincent; Molgora, Martina; Rodrigues, Patrick Fernandes; Nguyen, Khai M; Wang, Shoutang; Du, Siling; Wang, Wei-Le; Grajales-Reyes, Gary E; Ponce, Jennifer M; Yuede, Carla M; Li, Qingyun; Baer, John M; DeNardo, David G; Gilfillan, Susan; Cella, Marina; Satpathy, Ansuman T; Colonna, Marco.
Affiliation
  • Brioschi S; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA. Electronic address: s.brioschi@wustl.edu.
  • Belk JA; Department of Computer Science, Stanford University, Stanford, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
  • Peng V; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Molgora M; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Rodrigues PF; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Nguyen KM; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Wang S; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Du S; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Wang WL; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Grajales-Reyes GE; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Ponce JM; McDonnell Genome Institute, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Yuede CM; Department of Psychiatry, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Li Q; Department of Neuroscience, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA; Department of Genetics, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Baer JM; Department of Medicine, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • DeNardo DG; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA; Department of Medicine, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA; Siteman Cancer Center, Washington University School of Medicine in Saint Louis
  • Gilfillan S; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Cella M; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA.
  • Satpathy AT; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA; Department of Pathology, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Parker Institute for Cancer Immunotherapy, Stanford University, Stanford, CA, USA.
  • Colonna M; Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, USA. Electronic address: mcolonna@wustl.edu.
Immunity ; 56(5): 1027-1045.e8, 2023 05 09.
Article in En | MEDLINE | ID: mdl-36791722
Genetic tools to target microglia specifically and efficiently from the early stages of embryonic development are lacking. We generated a constitutive Cre line controlled by the microglia signature gene Crybb1 that produced nearly complete recombination in embryonic brain macrophages (microglia and border-associated macrophages [BAMs]) by the perinatal period, with limited recombination in peripheral myeloid cells. Using this tool in combination with Flt3-Cre lineage tracer, single-cell RNA-sequencing analysis, and confocal imaging, we resolved embryonic-derived versus monocyte-derived BAMs in the mouse cortex. Deletion of the transcription factor SMAD4 in microglia and embryonic-derived BAMs using Crybb1-Cre caused a developmental arrest of microglia, which instead acquired a BAM specification signature. By contrast, the development of genuine BAMs remained unaffected. Our results reveal that SMAD4 drives a transcriptional and epigenetic program that is indispensable for the commitment of brain macrophages to the microglia fate and highlight Crybb1-Cre as a tool for targeting embryonic brain macrophages.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Microglia / Macrophages Limits: Animals Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2023 Document type: Article Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Microglia / Macrophages Limits: Animals Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2023 Document type: Article Country of publication: United States