Phc2 controls hematopoietic stem and progenitor cell mobilization from bone marrow by repressing Vcam1 expression
| Autor: | Hyun Yong Jin, Chang Yong Choi, Chung Gyu Park, Kyoichi Isono, Kyungmin Park, Suk Jun Lee, Joonbeom Bae, Si Won Park, Young Sik Lee, Sang Hoon Kim, Taehoon Chun, Jihye Han, Haruhiko Koseki, Ji Yoon Lee, Han Hyoung Lee, Sang Pil Choi |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Stromal cell
Bone marrow transplantation Science Primary Cell Culture Vascular Cell Adhesion Molecule-1 General Physics and Astronomy Leukocyte homeostasis Epigenetic Repression Biology Article General Biochemistry Genetics and Molecular Biology Histones Mice Cell Movement medicine Animals Cell migration Epigenetics Progenitor cell lcsh:Science Cells Cultured Mice Knockout Multidisciplinary Haematopoietic stem cells Hematopoietic Stem Cell Transplantation Polycomb Repressive Complex 2 General Chemistry DNA Methylation Hematopoietic Stem Cells Hematopoietic Stem Cell Mobilization Haematopoiesis medicine.anatomical_structure Cell culture Models Animal Cancer research lcsh:Q Bone marrow |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Mobilization of hematopoietic stem and progenitor cells (HSPCs) into the circulation is essential for maintaining homeostasis. Here, the authors show that Phc2 in bone marrow stromal cells represses the cell adhesion molecule Vcam1 and facilitates mobilization of HSPCs through regulation of epigenetic marks. |
| Databáze: | OpenAIRE |
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