Paediatrics Publications

Title

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

Authors

Xiaowei Chen, Columbia University Irving Medical Center
Huan Deng, Columbia University Irving Medical Center
Michael J. Churchill, Columbia University Irving Medical Center
Larry L. Luchsinger, Columbia University Irving Medical Center
Xing Du, Columbia University Irving Medical Center
Timothy H. Chu, Columbia University Irving Medical Center
Richard A. Friedman, Columbia University Irving Medical Center
Moritz Middelhoff, Columbia University Irving Medical Center
Hongxu Ding, Columbia University Irving Medical Center
Yagnesh H. Tailor, Columbia University Irving Medical Center
Alexander L.E. Wang, Columbia University Irving Medical Center
Haibo Liu, Columbia University Irving Medical Center
Zhengchuan Niu, Columbia University Irving Medical Center
Hongshan Wang, Columbia University Irving Medical Center
Zhenyu Jiang, Columbia University Irving Medical Center
Simon Renders, Columbia University Irving Medical Center
Siu Hong Ho, Columbia University Irving Medical Center
Spandan V. Shah, Columbia University Irving Medical Center
Pavel Tishchenko, Columbia University Irving Medical Center
Wenju Chang, Columbia University Irving Medical Center
Theresa C. Swayne, Columbia University Irving Medical Center
Laura Munteanu, Columbia University Irving Medical Center
Andrea Califano, Columbia University Irving Medical Center
Ryota Takahashi, Columbia University Irving Medical Center
Karan K. Nagar, Columbia University Irving Medical Center
Bernhard W. Renz, Columbia University Irving Medical Center
Daniel L. Worthley, Columbia University Irving Medical Center
C. Benedikt Westphalen, Columbia University Irving Medical Center
Yoku Hayakawa, Columbia University Irving Medical Center

Document Type

Article

Publication Date

12-7-2017

Journal

Cell Stem Cell

Volume

21

Issue

6

First Page

747

Last Page

760.e7

URL with Digital Object Identifier

10.1016/j.stem.2017.11.003

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. 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.

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