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

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...

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Autores principales: 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, Chung-Gyu, Koseki, Haruhiko, Lee, Young Sik, Chun, Taehoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677815/
https://www.ncbi.nlm.nih.gov/pubmed/31375680
http://dx.doi.org/10.1038/s41467-019-11386-4
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author 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, Chung-Gyu
Koseki, Haruhiko
Lee, Young Sik
Chun, Taehoon
author_facet 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, Chung-Gyu
Koseki, Haruhiko
Lee, Young Sik
Chun, Taehoon
author_sort Bae, Joonbeom
collection PubMed
description 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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spelling pubmed-66778152019-08-05 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, Chung-Gyu Koseki, Haruhiko Lee, Young Sik Chun, Taehoon Nat Commun Article 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. Nature Publishing Group UK 2019-08-02 /pmc/articles/PMC6677815/ /pubmed/31375680 http://dx.doi.org/10.1038/s41467-019-11386-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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, Chung-Gyu
Koseki, Haruhiko
Lee, Young Sik
Chun, Taehoon
Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression
title Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression
title_full Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression
title_fullStr Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression
title_full_unstemmed Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression
title_short Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression
title_sort phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing vcam1 expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677815/
https://www.ncbi.nlm.nih.gov/pubmed/31375680
http://dx.doi.org/10.1038/s41467-019-11386-4
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