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

Chen, Xiaowei; Deng, Huan; Churchill, Michael J.; Luchsinger, Larry L.; Du, Xing; Chu, Timothy H.; Friedman, Richard A.; Middelhoff, Moritz; Ding, Hongxu; Tailor, Yagnesh H.; Wang, Alexander L. E.; Liu, Haibo; Niu, Zhengchuan; Wang, Hongshan; Jiang, Zhenyu; Renders, Simon; Ho, Siu-Hong; Shah, Spandan V.; Tishchenko, Pavel; Chang, Wenju; Swayne, Theresa C.; Munteanu, Laura; Califano, Andrea; Takahashi, Ryota; Nagar, Karan K.; Renz, Bernhard W.; Worthley, Daniel L.; Westphalen, C. Benedikt; Hayakawa, Yoku; Asfaha, Samuel; Borot, Florence; Lin, Chyuan-Sheng; Snöck, Hans-Willem; Mukherjee, Siddhartha and Wang, Timothy C. (2017): Bone Marrow Myeloid Cells Regulate Myeloid-Biased Hematopoietic Stem Cells via a Histamine-Dependent Feedback Loop. In: Cell Stem Cell, Vol. 21, No. 6: pp. 747-760

Abstract

Myeloid-biased hematopoietic stem cells (MBHSCs) 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 H-2 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 H-2 agonist protects MB-HSCs from depletion after sepsis. Thus, histamine couples lineage-specific physiological demands to intrinsically primed MBHSCs to enforce homeostasis.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1934-5909
• Language: English