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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.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Chen X,Deng H,Churchill MJ,Luchsinger LL,Du X,Chu TH,Friedman RA,Middelhoff M,Ding H,Tailor YH,Wang ALE,Liu H,Niu Z,Wang H,Jiang Z,Renders S,Ho SH,Shah SV,Tishchenko P,Chang W,Swayne TC,Munteanu L,Califano A,

doi

10.1016/j.stem.2017.11.003

subject

Has Abstract

pub_date

2017-12-07 00:00:00

pages

747-760.e7

issue

6

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(17)30455-1

journal_volume

21

pub_type

杂志文章

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