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; Taehoon Chun

doi:10.1038/s41467-019-11386-4

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, Taehoon Chun

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11 Citations (Scopus)

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.

Original language	English
Article number	3496
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11386-4
Publication status	Published - 2019 Dec 1

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Bae, J., Choi, S. P., Isono, K., Lee, J. Y., Park, S. W., Choi, C. Y., Han, J., Kim, S. H., Lee, H. H., Park, K., Jin, H. Y., Lee, S. J., Park, C. G., Koseki, H., Lee, Y. S., & Chun, T. (2019). Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression. Nature communications, 10(1), Article 3496. https://doi.org/10.1038/s41467-019-11386-4

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title = "Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression",

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.",

author = "Joonbeom Bae and Choi, {Sang Pil} and Kyoichi Isono and Lee, {Ji Yoon} and Park, {Si Won} and Choi, {Chang Yong} and Jihye Han and Kim, {Sang Hoon} and Lee, {Han Hyoung} and Kyungmin Park and Jin, {Hyun Yong} and Lee, {Suk Jun} and Park, {Chung Gyu} and Haruhiko Koseki and Lee, {Young Sik} and Taehoon Chun",

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AU - Park, Si Won

AU - Choi, Chang Yong

AU - Han, Jihye

AU - Kim, Sang Hoon

AU - Lee, Han Hyoung

AU - Park, Kyungmin

AU - Jin, Hyun Yong

AU - Lee, Suk Jun

AU - Park, Chung Gyu

AU - Koseki, Haruhiko

AU - Lee, Young Sik

AU - Chun, Taehoon

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

Abstract

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ASJC Scopus subject areas

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