한빛사 논문
Joonbeom Bae1,8, Sang-Pil Choi1,8, Kyoichi Isono2, Ji Yoon Lee3, Si-Won Park1, Chang-Yong Choi1, Jihye Han1, Sang-Hoon Kim1, Han-Hyoung Lee1, Kyungmin Park1, Hyun Yong Jin4, Suk Jun Lee5, Chung-Gyu Park6, Haruhiko Koseki7, Young Sik Lee1 & Taehoon Chun1,*
1Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea. 2Laboratory Animal Center, Wakayama Medical University, Wakayama 641-8509, Japan. 3Department of Biomedical Science, CHA University, Seongnam, Gyounggi-do 13488, Republic of Korea. 4Department of Urology, School of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA. 5Department of Biomedical Laboratory Science, College of Health Science, Cheongju University, Cheongju-si 28503, Republic of Korea. 6Department of Microbiology and Immunology, Cancer Research Institute and Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul 03087, Republic of Korea. 7Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan. 8These authors contributed equally: Joonbeom Bae, Sang-Pil Choi.
*Correspondence and requests for materials should be addressed to T.C.
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.
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