Bmi1 restricts the adipogenic differentiation of bone marrow stromal cells to maintain the integrity of the hematopoietic stem cell niche.
- Resource Type
- Academic Journal
- Authors
- Kato Y; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Life Science, Faculty of Medicine, Shimane University, Izumo City, Shimane, Japan; PuREC Company, Ltd., Izumo City, Shimane, Japan.; Hou LB; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.; Miyagi S; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Life Science, Faculty of Medicine, Shimane University, Izumo City, Shimane, Japan.; Nitta E; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan; Division of Structural Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Hyogo, Japan.; Aoyama K; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.; Shinoda D; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan; Division of Stem Cell and Molecular Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.; Yamazaki S; Division of Stem Cell Biology, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.; Kuribayashi W; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan; Division of Stem Cell and Molecular Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.; Isshiki Y; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.; Koide S; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan; Division of Stem Cell and Molecular Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.; Si S; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.; Saraya A; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.; Matsuzaki Y; Department of Life Science, Faculty of Medicine, Shimane University, Izumo City, Shimane, Japan; PuREC Company, Ltd., Izumo City, Shimane, Japan.; van Lohuizen M; Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Amsterdam, The Netherlands.; Iwama A; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan; Division of Stem Cell and Molecular Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan. Electronic address: 03aiwama@ims.u-tokyo.ac.jp.
- Source
- Publisher: Elsevier Science Inc Country of Publication: Netherlands NLM ID: 0402313 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2399 (Electronic) Linking ISSN: 0301472X NLM ISO Abbreviation: Exp Hematol Subsets: MEDLINE
- Subject
- Language
- English
The polycomb group protein Bmi1 maintains hematopoietic stem cell (HSC) functions. We previously reported that Bmi1-deficient mice exhibited progressive fatty changes in bone marrow (BM). A large portion of HSCs reside in the perivascular niche created partly by endothelial cells and leptin receptor + (LepR + ) BM stromal cells. To clarify how Bmi1 regulates the HSC niche, we specifically deleted Bmi1 in LepR + cells in mice. The Bmi1 deletion promoted the adipogenic differentiation of LepR + stromal cells and caused progressive fatty changes in the BM of limb bones with age, resulting in reductions in the numbers of HSCs and progenitors in BM and enhanced extramedullary hematopoiesis. This adipogenic change was also evident during BM regeneration after irradiation. Several adipogenic regulator genes appeared to be regulated by Bmi1. Our results indicate that Bmi1 keeps the adipogenic differentiation program repressed in BM stromal cells to maintain the integrity of the HSC niche.
(Copyright © 2019 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)