Differential regulation of fetal bone marrow and liver hematopoiesis by yolk-sac-derived myeloid cells
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 and
Daniel Lucas ()
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Benjamin Weinhaus: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center
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
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
Jizhou Zhang: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center
Qingqing Wu: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center
J. Matthew Kofron: Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center
Ty D. Troutman: Department of Pediatrics, University of Cincinnati College of Medicine
Tony DeFalco: Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center
Daniel Lucas: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Medical Center
Nature Communications, 2025, vol. 16, issue 1, 1-13
Abstract:
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.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59058-w
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DOI: 10.1038/s41467-025-59058-w
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