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


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.

SUBMITTER: Chen X 

PROVIDER: S-EPMC5975960 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Chen Xiaowei X   Deng Huan H   Churchill Michael J MJ   Luchsinger Larry L LL   Du Xing X   Chu Timothy H TH   Friedman Richard A RA   Middelhoff Moritz M   Ding Hongxu H   Tailor Yagnesh H YH   Wang Alexander L E ALE   Liu Haibo H   Niu Zhengchuan Z   Wang Hongshan H   Jiang Zhengyu Z   Renders Simon S   Ho Siu-Hong SH   Shah Spandan V SV   Tishchenko Pavel P   Chang Wenju W   Swayne Theresa C TC   Munteanu Laura L   Califano Andrea A   Takahashi Ryota R   Nagar Karan K KK   Renz Bernhard W BW   Worthley Daniel L DL   Westphalen C Benedikt CB   Hayakawa Yoku Y   Asfaha Samuel S   Borot Florence F   Lin Chyuan-Sheng CS   Snoeck Hans-Willem HW   Mukherjee Siddhartha S   Wang Timothy C TC  

Cell stem cell 20171130 6


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<sup>+</sup> myeloid cells lie in close anatomical proximity to MB-HSCs and produce histamine, which activates the H<sub>2</sub> receptor on MB-HSCs t  ...[more]

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