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Differential regulation of fetal bone marrow and liver hematopoiesis by yolk-sac-derived myeloid cells

Author

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  • Benjamin Weinhaus

    (Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center
    Immunology Graduate Program, University of Cincinnati College of Medicine)

  • Shelli Homan

    (Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center)

  • Morgan Kincaid

    (Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center)

  • Aryan Tadwalkar

    (Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center)

  • Xiaowei Gu

    (Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center
    University of Science and Technology of China)

  • Sumit Kumar

    (Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center)

  • Anastasiya Slaughter

    (Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center
    Immunology Graduate Program, University of Cincinnati College of Medicine)

  • Jizhou Zhang

    (Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center
    University of Science and Technology of China)

  • Qingqing Wu

    (Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center
    University of Science and Technology of China)

  • J. Matthew Kofron

    (Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center
    Department of Pediatrics, University of Cincinnati College of Medicine)

  • Ty D. Troutman

    (Department of Pediatrics, University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center)

  • Tony DeFalco

    (Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center
    Department of Pediatrics, University of Cincinnati College of Medicine)

  • Daniel Lucas

    (Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center
    Department of Pediatrics, University of Cincinnati College of Medicine)

Abstract

Fetal hematopoiesis takes place in the liver before colonizing the bone marrow where it will persist for life. This colonization is thought to be mediated by specification of a microenvironment that selectively recruits hematopoietic cells to the nascent bone marrow. The identity and mechanisms regulating the specification of this colonization niche are unclear. Here we identify a VCAM1+ sinusoidal colonization niche in the diaphysis that regulates neutrophil and hematopoietic stem cell colonization of the bone marrow. Using confocal microscopy, we find that colonizing hematopoietic stem and progenitor cells (HSPC) and myeloid cells selectively localize to a subset of VCAM1+ sinusoids in the center of the diaphysis. Vcam1 deletion in endothelial cells impairs hematopoietic colonization while depletion of yolk-sac-derived osteoclasts disrupts VCAM1+ expression, and impairs neutrophil and HSPC colonization to the bone marrow. Depletion of yolk-sac-derived myeloid cells increases fetal liver hematopoietic stem cell numbers, function and erythropoiesis independent of osteoclast activity. Thus, the yolk sac produces myeloid cells that have opposite roles in fetal hematopoiesis: while yolk-sac derived myeloid cells in the bone marrow promote hematopoietic colonization by specifying a VCAM1+ colonization niche, a different subset of yolk-sac-derived myeloid cells inhibits HSC in the fetal liver.

Suggested Citation

  • Benjamin Weinhaus & Shelli Homan & Morgan Kincaid & Aryan Tadwalkar & Xiaowei Gu & Sumit Kumar & Anastasiya Slaughter & Jizhou Zhang & Qingqing Wu & J. Matthew Kofron & Ty D. Troutman & Tony DeFalco &, 2025. "Differential regulation of fetal bone marrow and liver hematopoiesis by yolk-sac-derived myeloid cells," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59058-w
    DOI: 10.1038/s41467-025-59058-w
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