Pathogenic role of niche aging in the development of age-associated hematological malignancies
Description: 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. Our results indicate that Bmi1 keeps the adipogenic differentiation program repressed in BM stromal cells to maintain the integrity of the HSC niche.
Amount: ¥6,370,000
Funding type: research
Funder scheme: Grant-in-Aid for Challenging Research (Exploratory)
Start date: 2018-06-29
End date: 2020-03-31
Investigator: Atsushi Iwama
Institution: The University of Tokyo
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 6
Funder award ID: 18K19555
OpenAlex ID: G6779635035