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, Chunggyu Park, Haruhiko Koseki, Young Sik Lee, Taehoon Chun

Research output: Contribution to journalArticle

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 languageEnglish
Article number3496
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2019

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Hematopoietic Stem Cell Mobilization
bone marrow
stem cells
Hematopoietic Stem Cells
Bone
Bone Marrow
stems
cells
Tissue homeostasis
mice
Vascular Cell Adhesion Molecule-1
Ablation
Modulators
Mesenchymal Stromal Cells
homeostasis
Epigenomics
leukocytes
Tuning
regulators
Tissue

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Bae, Joonbeom ; Choi, Sang Pil ; Isono, Kyoichi ; Lee, Ji Yoon ; Park, Si Won ; Choi, Chang Yong ; Han, Jihye ; Kim, Sang Hoon ; Lee, Han Hyoung ; Park, Kyungmin ; Jin, Hyun Yong ; Lee, Suk Jun ; Park, Chunggyu ; Koseki, Haruhiko ; Lee, Young Sik ; Chun, Taehoon. / Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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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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Bae, J, Choi, SP, Isono, K, Lee, JY, Park, SW, Choi, CY, Han, J, Kim, SH, Lee, HH, Park, K, Jin, HY, Lee, SJ, Park, C, Koseki, H, Lee, YS & Chun, T 2019, 'Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression', Nature Communications, vol. 10, no. 1, 3496. https://doi.org/10.1038/s41467-019-11386-4

Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression. / Bae, Joonbeom; Choi, Sang Pil; Isono, Kyoichi; Lee, Ji Yoon; Park, Si Won; Choi, Chang Yong; Han, Jihye; Kim, Sang Hoon; Lee, Han Hyoung; Park, Kyungmin; Jin, Hyun Yong; Lee, Suk Jun; Park, Chunggyu; Koseki, Haruhiko; Lee, Young Sik; Chun, Taehoon.

In: Nature Communications, Vol. 10, No. 1, 3496, 01.12.2019.

Research output: Contribution to journalArticle

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T1 - Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression

AU - Bae, Joonbeom

AU - Choi, Sang Pil

AU - Isono, Kyoichi

AU - Lee, Ji Yoon

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, Chunggyu

AU - Koseki, Haruhiko

AU - Lee, Young Sik

AU - Chun, Taehoon

PY - 2019/12/1

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