We also found that thrombopoietin has a pivotal role in determining total HSC numbers in the body, even in the context of increased niche availability. Our study provides new insights into stem cell number regulation and opens avenues of investigation into various fields. (6/6)

Moreover, HSC numbers in transplanted wild-type femurs did not exceed physiological levels when HSCs were mobilized from defective endogenous niches to the periphery, indicating that HSC numbers are constrained at the local level as well. (5/6)

To test this, we developed a femur-transplantation system, enabling us to increase HSC niche cells without adding HSCs. Surprisingly, adding niches did not increase the total HSC numbers in the body, revealing the presence of systemic mechanism(s) that limits HSC numbers. (4/6)

We and others have previously identified several HSC niche components, including mesenchymal stem cells in the bone marrow. However, their numbers significantly exceed HSC numbers, leading us to hypothesize that other regulatory mechanisms govern HSC numbers. (3/6)

HSCs play a major role in blood cell production, making the regulation of HSC numbers a central question in stem cell biology. A model from the 1970s suggested that HSC numbers are determined locally by the availability of their bone marrow microenvironments, or niches. (2/6)

Thank you, Ann!

Thanks so much, Daniel!

Thank you, Divij!

Thank you, Ravi!