title: Specification of tissue-resident macrophages during organogenesis.
abstract: Tissue-resident macrophages support embryonic development and tissue homeostasis and repair. The mechanisms that control their differentiation remain unclear. We report here that erythro-myeloid progenitors in mice generate premacrophages (pMacs) that simultaneously colonize the whole embryo from embryonic day 9.5 in a chemokine-receptor-dependent manner. The core macrophage program initiated in pMacs is rapidly diversified as expression of transcriptional regulators becomes tissue-specific in early macrophages. This process appears essential for macrophage specification and maintenance, as inactivation of Id3 impairs the development of liver macrophages and results in selective Kupffer cell deficiency in adults. We propose that macrophage differentiation is an integral part of organogenesis, as colonization of organ anlagen by pMacs is followed by their specification into tissue macrophages, hereby generating the macrophage diversity observed in postnatal tissues.
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors: Elvira
authors: E
authors: Mass
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors: Ivan
authors: I
authors: Ballesteros
authors: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
authors: Matthias
authors: M
authors: Farlik
authors: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
authors: Florian
authors: F
authors: Halbritter
authors: Genomics & Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors: Patrick
authors: P
authors: Günther
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.|Weill Cornell Graduate School of Medical Sciences, New York, New York, USA.
authors: Lucile
authors: L
authors: Crozet
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors: Christian E
authors: CE
authors: Jacome-Galarza
authors: Genomics & Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors: Kristian
authors: K
authors: Händler
authors: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
authors: Johanna
authors: J
authors: Klughammer
authors: Institute for Oral Science, Matsumoto Dental University, 1780 Hiro-Oka Gobara Shiojiri, Nagano, 390-0781 Japan.
authors: Yasuhiro
authors: Y
authors: Kobayashi
authors: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King's College London, London SE1 1UL, UK.
authors: Elisa
authors: E
authors: Gomez-Perdiguero
authors: Genomics & Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.|Single Cell Genomics and Epigenomics Unit at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
authors: Joachim L
authors: JL
authors: Schultze
authors: Genomics & Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.|Single Cell Genomics and Epigenomics Unit at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
authors: Marc
authors: M
authors: Beyer
authors: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.|Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.|Max Planck Institute for Informatics, 66123 Saarbrücken, Germany.
authors: Christoph
authors: C
authors: Bock
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.|Weill Cornell Graduate School of Medical Sciences, New York, New York, USA.|Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King's College London, London SE1 1UL, UK.
authors: Frederic
authors: F
authors: Geissmann
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology*; D047108:Embryonic Development; D004627:Embryonic Induction; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism; D007728:Kupffer Cells / Q000166:cytology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D009928:Organ Specificity; D038081:Organogenesis; D019707:Receptors, Chemokine / Q000235:genetics; D059467:Transcriptome
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D051796:Inhibitor of Differentiation Proteins; D019707:Receptors, Chemokine; C067679:Idb3 protein, mouse