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.

中文翻译：

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骨髓髓系细胞通过组胺依赖性反馈回路调节偏向髓系的造血干细胞。

偏向骨髓的造血干细胞 (MB-HSC) 在损伤恢复中起着关键作用，但人们对它们在骨髓生态位中的调节方式知之甚少。在这里，我们描述了一种自体/旁分泌生理回路，它控制 MB-HSC 和以组氨酸脱羧酶 (Hdc) 为标记的造血祖细胞的静止。定型 Hdc ⁺髓样细胞在解剖学上靠近 MB-HSC，并产生组胺，激活 H ₂MB-HSCs 上的受体以促进它们的静止和自我更新。耗尽产生组胺的细胞会强制进入细胞周期，导致连续移植能力丧失，并使动物对化疗损伤敏感。通过脂多糖 (LPS) 处理增加对骨髓细胞的需求，特异性地将 MB-HSC 和祖细胞募集到细胞周期中；在没有组胺反馈的情况下，循环的 MB-HSC 无法恢复静止状态，导致它们耗尽，而 H ₂激动剂可保护 MB-HSC 在败血症后免于耗尽。因此，组胺将谱系特异性生理需求与内在启动的 MB-HSC 相结合，以加强体内平衡。