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

Joonbeom Bae, Sang-Pil Choi, Kyoichi Isono, Ji Yoon Lee, Si-Won Park, Chang-Yong Choi, Jihye Han, Sang-Hoon Kim, Han-Hyoung Lee, Kyungmin Park, Hyun Yong Jin, Suk Jun Lee, Chung-Gyu Park, Haruhiko Koseki, Young Sik Lee and Taehoon Chun ()
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Joonbeom Bae: Korea University
Sang-Pil Choi: Korea University
Kyoichi Isono: Wakayama Medical University
Ji Yoon Lee: CHA University
Si-Won Park: Korea University
Chang-Yong Choi: Korea University
Jihye Han: Korea University
Sang-Hoon Kim: Korea University
Han-Hyoung Lee: Korea University
Kyungmin Park: Korea University
Hyun Yong Jin: University of California, San Francisco
Suk Jun Lee: Cheongju University
Chung-Gyu Park: Seoul National University College of Medicine
Haruhiko Koseki: RIKEN Center for Integrative Medical Sciences
Young Sik Lee: Korea University
Taehoon Chun: Korea University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-11386-4

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