Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression

被引：12

作者：

Bae, Joonbeom ^{[1
]}

Choi, Sang-Pil ^{[1
]}

Isono, Kyoichi ^{[2
]}

Lee, Ji Yoon ^{[3
]}

Park, Si-Won ^{[1
]}

Choi, Chang-Yong ^{[1
]}

Han, Jihye ^{[1
]}

Kim, Sang-Noon ^{[1
]}

Lee, Han-Hyoung ^{[1
]}

Park, Kyungmin ^{[1
]}

Jin, Hyun Yong ^{[4
]}

Lee, Suk Jun ^{[5
]}

Park, Chung-Gyu ^{[6
,7
]}

Koseki, Haruhiko ^{[8
]}

Lee, Young Sik ^{[1
]}

Chun, Taehoon ^{[1
]}

机构：

[1] Korea Univ, Coll Life Sci & Biotechnol, Dept Biotechnol, Seoul 02841, South Korea

[2] Wakayama Med Univ, Lab Anim Ctr, Wakayama 6418509, Japan

[3] CHA Univ, Dept Biomed Sci, Seongnam 13488, Gyounggi Do, South Korea

[4] Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94158 USA

[5] Cheongju Univ, Coll Hlth Sci, Dept Biomed Lab Sci, Cheongju 28503, South Korea

[6] Seoul Natl Univ, Canc Res Inst, Dept Microbiol & Immunol, Coll Med, Seoul 03087, South Korea

[7] Seoul Natl Univ, Coll Med, Xenotransplantat Res Ctr, Seoul 03087, South Korea

[8] RIKEN, Lab Dev Genet, Ctr Integrat Med Sci, Yokohama, Kanagawa 2300045, Japan

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

新加坡国家研究基金会;

关键词：

ADHESION MOLECULE-1; POLYCOMB COMPLEXES; RAPID MOBILIZATION; FAMILY-MEMBERS; ACTIVATION; MEDIATE; NICHES; MICE; MAINTENANCE; METHYLATION;

D O I：

10.1038/s41467-019-11386-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The timely mobilization of hematopoietic stem and progenitor cells (HSPCs) is essential for maintaining hematopoietic and tissue leukocyte homeostasis. Understanding how HSPCs migrate between bone marrow (BM) and peripheral tissues is of great significance in the clinical setting, where therapeutic strategies for modulating their migration capacity determine the clinical outcome. Here, we identify an epigenetic regulator, Phc2, as a critical modulator of HSPC trafficking. The genetic ablation of Phc2 in mice causes a severe defect in HSPC mobilization through the derepression of Vcam1 in bone marrow stromal cells (BMSCs), ultimately leading to a systemic immunodeficiency. Moreover, the pharmacological inhibition of VCAM-1 in Phc2-deficient mice reverses the symptoms. We further determine that Phc2-dependent Vcam1 repression in BMSCs is mediated by the epigenetic regulation of H3K27me3 and H2AK119ub. Together, our data demonstrate a cell-extrinsic role for Phc2 in controlling the mobilization of HSPCs by finely tuning their bone marrow niche.

引用

页数：14

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