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|Title:||Bone marrow myeloid cells regulate myeloid-biased hematopoietic stem cells via a histamine-dependent feedback loop|
|Citation:||Cell Stem Cell, 2017; 21(6):747-760|
|Xiaowei Chen ... Daniel L. Worthley ... et al.|
|Abstract:||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 Hdc⁺ myeloid cells lie in close anatomical proximity to MB-HSCs and produce histamine, which activates the H₂ receptor 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 H₂ agonist protects MB-HSCs from depletion after sepsis. Thus, histamine couples lineage-specific physiological demands to intrinsically primed MB-HSCs to enforce homeostasis.|
|Keywords:||H2 receptor; bone marrow niche; hematopoietic stem cells; histamine; myeloid biased|
|Rights:||Copyright status unknown|
|Appears in Collections:||Medicine publications|
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