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Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations

Author

Listed:
  • Rocío Rojo

    (University of Edinburgh, Easter Bush
    Escuela de Medicina y Ciencias de la Salud)

  • Anna Raper

    (University of Edinburgh, Easter Bush)

  • Derya D. Ozdemir

    (University of Edinburgh, Easter Bush)

  • Lucas Lefevre

    (University of Edinburgh, Easter Bush)

  • Kathleen Grabert

    (University of Edinburgh, Easter Bush
    Karolinska Institutet)

  • Evi Wollscheid-Lengeling

    (University of Edinburgh, Easter Bush)

  • Barry Bradford

    (University of Edinburgh, Easter Bush)

  • Melanie Caruso

    (University of Edinburgh, Easter Bush)

  • Iveta Gazova

    (University of Edinburgh, Easter Bush)

  • Alejandra Sánchez

    (University of Edinburgh, Easter Bush)

  • Zofia M. Lisowski

    (University of Edinburgh, Easter Bush)

  • Joana Alves

    (University of Edinburgh, Easter Bush)

  • Irene Molina-Gonzalez

    (The Queen’s Medical Research Institute)

  • Hayk Davtyan

    (University of California Irvine)

  • Rebecca J. Lodge

    (The Queen’s Medical Research Institute)

  • James D. Glover

    (University of Edinburgh, Easter Bush)

  • Robert Wallace

    (University of Edinburgh)

  • David A. D. Munro

    (The University of Edinburgh)

  • Eyal David

    (Weizmann Institute of Science)

  • Ido Amit

    (Weizmann Institute of Science)

  • Véronique E. Miron

    (The Queen’s Medical Research Institute)

  • Josef Priller

    (The University of Edinburgh)

  • Stephen J. Jenkins

    (The Queen’s Medical Research Institute)

  • Giles E. Hardingham

    (The University of Edinburgh
    University of Edinburgh)

  • Mathew Blurton-Jones

    (University of California Irvine)

  • Neil A. Mabbott

    (University of Edinburgh, Easter Bush)

  • Kim M. Summers

    (Translational Research Institute)

  • Peter Hohenstein

    (University of Edinburgh, Easter Bush
    Leiden University Medical Center)

  • David A. Hume

    (Translational Research Institute)

  • Clare Pridans

    (The Queen’s Medical Research Institute
    University of Edinburgh)

Abstract

The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. The mammalian Csf1r locus contains a highly conserved super-enhancer, the fms-intronic regulatory element (FIRE). Here we show that genomic deletion of FIRE in mice selectively impacts CSF1R expression and tissue macrophage development in specific tissues. Deletion of FIRE ablates macrophage development from murine embryonic stem cells. Csf1rΔFIRE/ΔFIRE mice lack macrophages in the embryo, brain microglia and resident macrophages in the skin, kidney, heart and peritoneum. The homeostasis of other macrophage populations and monocytes is unaffected, but monocytes and their progenitors in bone marrow lack surface CSF1R. Finally, Csf1rΔFIRE/ΔFIRE mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r−/− rodents. Csf1rΔFIRE/ΔFIRE mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals.

Suggested Citation

  • Rocío Rojo & Anna Raper & Derya D. Ozdemir & Lucas Lefevre & Kathleen Grabert & Evi Wollscheid-Lengeling & Barry Bradford & Melanie Caruso & Iveta Gazova & Alejandra Sánchez & Zofia M. Lisowski & Joan, 2019. "Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11053-8
    DOI: 10.1038/s41467-019-11053-8
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    Cited by:

    1. Jingbo Qie & Yang Liu & Yunzhi Wang & Fan Zhang & Zhaoyu Qin & Sha Tian & Mingwei Liu & Kai Li & Wenhao Shi & Lei Song & Mingjun Sun & Yexin Tong & Ping Hu & Tao Gong & Xiaqiong Wang & Yi Huang & Bolo, 2022. "Integrated proteomic and transcriptomic landscape of macrophages in mouse tissues," Nature Communications, Nature, vol. 13(1), pages 1-23, December.

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