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Bone Marrow Myeloid Cells Regulate Myeloid-Biased Hematopoietic Stem Cells via a Histamine-Dependent Feedback Loop.

Cell stem cell | 2017

Myeloid-biased hematopoietic stem cells (MB-HSCs) play critical roles in recovery from injury, but little is known about how they are regulated within the bone marrow niche. Here we describe an auto-/paracrine physiologic circuit that controls quiescence of MB-HSCs and hematopoietic progenitors marked by histidine decarboxylase (Hdc). Committed Hdcmyeloid cells lie in close anatomical proximity to MB-HSCs and produce histamine, which activates the Hreceptor on MB-HSCs to promote their quiescence and self-renewal. Depleting histamine-producing cells enforces cell cycle entry, induces loss of serial transplant capacity, and sensitizes animals to chemotherapeutic injury. Increasing demand for myeloid cells via lipopolysaccharide (LPS) treatment specifically recruits MB-HSCs and progenitors into the cell cycle; cycling MB-HSCs fail to revert into quiescence in the absence of histamine feedback, leading to their depletion, while an Hagonist protects MB-HSCs from depletion after sepsis. Thus, histamine couples lineage-specific physiological demands to intrinsically primed MB-HSCs to enforce homeostasis.

Pubmed ID: 29198940 RIS Download

Mesh terms: Animals | Bone Marrow | Bone Marrow Transplantation | Flow Cytometry | Hematopoietic Stem Cells | Histamine | Lipopolysaccharides | Mice | Myeloid Cells

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Associated grants

  • Agency: NCRR NIH HHS, United States
    Id: S10 RR027050
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL135039
  • Agency: NIH HHS, United States
    Id: S10 OD012351
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK048077
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL115145
  • Agency: NIH HHS, United States
    Id: S10 OD020056
  • Agency: NCI NIH HHS, United States
    Id: P30 CA013696
  • Agency: NIH HHS, United States
    Id: S10 OD021764
  • Agency: NCI NIH HHS, United States
    Id: R35 CA197745

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