Gao Xin, Zhang Jing, Tamplin Owen J
Wisconsin Blood Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, United States.
McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, United States.
Front Hematol. 2025;4. doi: 10.3389/frhem.2025.1525132. Epub 2025 Feb 6.
Hematopoietic stem cells (HSCs) undergo a functional decline during aging. The intrinsic characteristics of aged HSCs have been well-described and include a strong myeloid bias, an increase in total number, and a decrease in functionality during transplantation. The impact of the aged bone marrow microenvironment, or niche, on HSCs is less well understood. It is critical to understand the changing condition of the niche during aging, and its ability to support HSCs, as this could reveal the very signals and mechanisms needed to improve HSC fitness. Furthermore, heterochronic transplantation provides an approach to test the influence of an aged recipient niche on young donor HSCs, and conversely, of a young recipient niche on aged donor HSCs. Importantly, these experiments demonstrated that donor HSC engraftment is reduced if the recipient niche is aged, and conversely, the young niche can rejuvenate aged donor HSCs. Here we will focus on the interactions between aged HSCs and their microenvironment. We will highlight current controversies, research gaps, and future directions.
造血干细胞(HSCs)在衰老过程中会出现功能衰退。衰老造血干细胞的内在特征已得到充分描述,包括强烈的髓系偏向、总数增加以及移植过程中功能下降。衰老的骨髓微环境或生态位对造血干细胞的影响尚不太清楚。了解衰老过程中生态位的变化情况及其支持造血干细胞的能力至关重要,因为这可能揭示改善造血干细胞健康所需的信号和机制。此外,异时移植提供了一种方法来测试衰老受体生态位对年轻供体造血干细胞的影响,反之,年轻受体生态位对衰老供体造血干细胞的影响。重要的是,这些实验表明,如果受体生态位衰老,供体造血干细胞的植入会减少,反之,年轻的生态位可以使衰老的供体造血干细胞恢复活力。在这里,我们将重点关注衰老造血干细胞与其微环境之间的相互作用。我们将突出当前的争议、研究空白和未来方向。