1. Bmi1 restricts the adipogenic differentiation of bone marrow stromal cells to maintain the integrity of the hematopoietic stem cell niche
- Author
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Yusuke Isshiki, Daisuke Shinoda, Sha Si, Shuhei Koide, Eriko Nitta, Satoru Miyagi, Maarten van Lohuizen, Satoshi Yamazaki, Atsunori Saraya, Atsushi Iwama, Li-Bo Hou, Wakako Kuribayashi, Yuko Kato, Yumi Matsuzaki, and Kazumasa Aoyama
- Subjects
0301 basic medicine ,Cancer Research ,Stromal cell ,Hematopoietic stem cell niche ,macromolecular substances ,Biology ,Cell Line ,03 medical and health sciences ,Mice ,Mice, Congenic ,0302 clinical medicine ,Bone Marrow ,Proto-Oncogene Proteins ,Genetics ,medicine ,Animals ,Regeneration ,Progenitor cell ,Cell Self Renewal ,Stem Cell Niche ,Molecular Biology ,Mice, Knockout ,Polycomb Repressive Complex 1 ,Leptin receptor ,Adipogenesis ,Gene Expression Profiling ,Hematopoietic stem cell ,Gene Expression Regulation, Developmental ,Cell Biology ,Hematology ,Hematopoietic Stem Cells ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,BMI1 ,030220 oncology & carcinogenesis ,Receptors, Leptin ,Bone marrow ,Stromal Cells - Abstract
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.
- Published
- 2019