Stable platelet production via the bypass pathway explains long-term hematopoietic stem cell reconstitution

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-04-29 DOI:10.1016/j.isci.2025.112547

Shoya Iwanami , Toshiko Sato , Hiroshi Haeno , Longchen Xu , Keimyo Imamura , Jun Ooehara , Xun Lan , Hiromitsu Nakauchi , Shingo Iwami , Ryo Yamamoto

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引用次数: 0

Abstract

In vivo differentiation pathways into several blood cell lineages of Hematopoietic stem cells (HSCs) remain challenging to track over time. Using data from single-cell transplantation assays and mathematical modeling, we examined HSC differentiation kinetics, including the myeloid bypass pathway. We found that myeloid cell production was unchanged with age, whereas B cell production declined, quantitatively confirming myeloid lineage skewing. Estimated dependence on the platelet-bypass correlated with the long-term reconstitution capacity of HSCs. Time-dependent blood cell production patterns calculated by our model distinguished the reconstitution potential of HSCs into subgroups, suggesting a link between the bypass pathway and the multilineage differentiation dynamics of HSCs. Notably, platelet bypass dependence could be determined by the platelet-to-erythrocyte chimerism ratio at 8 weeks after transplantation, serving as a predictive indicator of long-term HSC function. These findings provide quantitative insights into HSC aging and differentiation dynamics, emphasizing the role of the bypass pathway in defining HSC properties.

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通过旁路途径稳定的血小板生成解释了长期的造血干细胞重建

随着时间的推移，造血干细胞（hsc）在体内分化为几种血细胞谱系的途径仍然具有挑战性。利用单细胞移植试验和数学模型的数据，我们检查了HSC分化动力学，包括骨髓旁路通路。我们发现骨髓细胞的产量随年龄的增长而不变，而B细胞的产量下降，定量地证实了骨髓谱系的倾斜。估计对血小板旁路的依赖与造血干细胞的长期重建能力相关。通过我们的模型计算的时间依赖性血细胞生成模式将造血干细胞的重构潜力区分为亚组，这表明旁路通路与造血干细胞的多谱系分化动力学之间存在联系。值得注意的是，血小板旁路依赖性可以通过移植后8周的血小板与红细胞嵌合比率来确定，作为长期HSC功能的预测指标。这些发现为HSC老化和分化动力学提供了定量的见解，强调了旁路通路在定义HSC特性中的作用。

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

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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