Aberrant engagement of P-selectin drives hematopoietic stem cell aging in mice.

IF 17 Q1 CELL BIOLOGY
Nature aging Pub Date : 2025-06-01 Epub Date: 2025-05-23 DOI:10.1038/s43587-025-00880-8
Daozheng Yang, Natalia Skinder, Yun-Ruei Kao, Jiahao Chen, Victor Thiruthuvanathan, Arthur Flohr Svendsen, Chi Zhang, Bertien Dethmers-Ausema, Ellen Weersing, Maria Maryanovich, Britta Will, Gerald de Haan
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引用次数: 0

Abstract

During aging, hematopoietic stem cell (HSC) function progressively declines which can lead to reduced blood cell production and regeneration. This work uncovered that cell surface presentation of P-selectin (CD62P, encoded by Selp) increases in a large fraction of aging HSCs driven by a proinflammatory milieu in mice. Notably, expression of P-selectin molecularly and functionally dichotomized the aging HSC pool; stem cells presenting with highly abundant P-selectin were hallmarked by aging-associated gene expression programs and reduced repopulation capacity upon regenerative stress. Ectopic expression of Selp in young HSCs was sufficient to impair long-term reconstitution potential and impair erythropoiesis. Mechanistically, we uncovered that P-selectin receptor activation by its primary ligand, P-selectin glycoprotein ligand-1, suppressed aging-associated gene expression, and, reversely, lack of P-selectin signaling led to HSC premature aging. Collectively, our study uncovered a functional role of P-selectin engagement in regulating HSC regeneration and driving stem cell aging when perturbed.

p -选择素的异常参与驱动小鼠造血干细胞衰老。
在衰老过程中,造血干细胞(HSC)功能逐渐下降,这可能导致血细胞生成和再生减少。这项研究发现,在小鼠的促炎环境驱动下,p -选择素(由Selp编码的CD62P)的细胞表面呈现在很大一部分衰老hsc中增加。值得注意的是,p -选择素的表达在分子和功能上将衰老的HSC池一分为二;具有高度丰富p选择素的干细胞,其特征是衰老相关的基因表达程序和再生应激下再生能力的降低。年轻造血干细胞中Selp的异位表达足以损害长期重建潜力并损害红细胞生成。在机制上,我们发现p选择素受体被其初级配体p选择素糖蛋白配体-1激活,抑制衰老相关基因的表达,相反,p选择素信号的缺乏导致HSC过早衰老。总的来说,我们的研究揭示了p -选择素参与调节HSC再生和驱动干细胞衰老的功能作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
14.70
自引率
0.00%
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