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

Publication date: Available online 30 November 2017
Source:Cell Stem Cell
Author(s): Xiaowei Chen, Huan Deng, Michael J. Churchill, Larry L. Luchsinger, Xing Du, Timothy H. Chu, Richard A. Friedman, Moritz Middelhoff, Hongxu Ding, Yagnesh H. Tailor, Alexander L.E. Wang, Haibo Liu, Zhengchuan Niu, Hongshan Wang, Zhenyu Jiang, Simon Renders, Siu-Hong Ho, Spandan V. Shah, Pavel Tishchenko, Wenju Chang, Theresa C. Swayne, Laura Munteanu, Andrea Califano, Ryota Takahashi, Karan K. Nagar, Bernhard W. Renz, Daniel L. Worthley, C. Benedikt Westphalen, Yoku Hayakawa, Samuel Asfaha, Florence Borot, Chyuan-Sheng Lin, Hans-Willem Snoeck, Siddhartha Mukherjee, Timothy C. Wang
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.

Graphical abstract

Teaser

Chen et al. show that histidine decarboxylase (Hdc) marks quiescent myeloid-biased HSCs (MB-HSCs). Daughter myeloid cells form a spatial cluster with Hdc⁺ MB-HSCs and secrete histamine to enforce their quiescence and protect them from depletion, following activation by a variety of physiologic insults.


http://ift.tt/2ivcLWH