美国阿尔伯特·爱因斯坦医学院Ulrich Steidl研究组发现了造血干细胞的数量并不完全取决于生态位的可用性。相关论文于2025年8月27日发表于国际顶尖学术期刊《自然》杂志上。

为了严格定义生态位大小在调节HSC数量中的作用，研究小组开发了一个股骨移植系统，使他们能够增加可用的HSC生态位。值得注意的是，生态位的增加并没有改变体内的HSC总数，这表明存在一种限制HSC数量的系统机制。此外，当HSC从缺陷内源性壁龛转移到外周时，移植野生型股骨中的HSC数量没有超过生理水平，表明HSC数量在局部水平也受到限制。其他实验方法进一步支持了系统和局部双重限制的概念，包括异种共生和骨移植后造血干细胞的非条件转移。

此外，小组发现血小板生成素在决定体内造血干细胞总数方面起着关键作用，即使在生态位可用性增加的情况下也是如此。他们的研究重新定义了HSC数量调节的关键原则，为这一关键的生物学过程提供了见解。

研究人员表示，造血干细胞（HSC）存在于特定的微环境中，被称为生态位，经典模型表明，HSC的数量主要取决于生态位大小。然而，相对于造血干细胞的大量过剩的生态位细胞挑战了这一观点。

附：英文原文

Title: Haematopoietic stem cell number is not solely defined by niche availability

Author: Takeishi, Shoichiro, Marchand, Tony, Koba, Wade R., Borger, Daniel K., Xu, Chunliang, Guha, Chandan, Bergman, Aviv, Frenette, Paul S., Gritsman, Kira, Steidl, Ulrich

Issue&Volume: 2025-08-27

Abstract: Haematopoietic stem cells (HSCs) reside in specialized microenvironments, referred to as niches, and the classical model suggests that HSC numbers are predominantly determined by the niche size1,2,3,4,5. However, the vast excess of niche cells relative to HSCs challenges this perspective. To rigorously define the role of niche size in regulating HSC numbers, we developed a femur-transplantation system, enabling us to increase available HSC niches. Notably, the addition of niches did not alter the total HSC numbers in the body, suggesting the presence of a systemic mechanism that limits HSC numbers. Additionally, 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. The notion of dual restrictions at systemic and local levels was further supported by other experimental approaches, including parabiosis and non-conditioned transfer of HSCs after bone transplantation. Moreover, we found that thrombopoietin has a pivotal role in determining the total number of HSCs in the body, even in the context of increased niche availability. Our study redefines key principles underlying HSC number regulation, providing insights into this critical biological process.

DOI: 10.1038/s41586-025-09462-5

Source: https://www.nature.com/articles/s41586-025-09462-5