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Science. 2016 Sep 9;353(6304). pii: aaf4238. doi: 10.1126/science.aaf4238. Epub 2016 Aug 4.

Specification of tissue-resident macrophages during organogenesis.

Author information

1
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
2
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
3
Genomics & Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
4
Weill Cornell Graduate School of Medical Sciences, New York, New York, USA.
5
Institute for Oral Science, Matsumoto Dental University, 1780 Hiro-Oka Gobara Shiojiri, Nagano, 390-0781 Japan.
6
Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King's College London, London SE1 1UL, UK.
7
Single Cell Genomics and Epigenomics Unit at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
8
Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.
9
Max Planck Institute for Informatics, 66123 Saarbrücken, Germany.
#
Contributed equally

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.

Comment in

PMID:
27492475
PMCID:
PMC5066309
DOI:
10.1126/science.aaf4238
[Indexed for MEDLINE]
Free PMC Article

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