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Do haematopoietic stem cells age?
Nature Reviews Immunology ( IF 100.3 ) Pub Date : 2019-11-18 , DOI: 10.1038/s41577-019-0236-2
Kenneth Dorshkind 1 , Thomas Höfer 2 , Encarnacion Montecino-Rodriguez 1 , Peter D Pioli 1, 3 , Hans-Reimer Rodewald 4
Affiliation  

Genetic defects that accumulate in haematopoietic stem cells (HSCs) are thought to be responsible for age-related changes in haematopoiesis that include a decline in lymphopoiesis and skewing towards the myeloid lineage. This HSC-centric view is based largely on studies showing that HSCs from aged mice exhibit these lineage biases following transplantation into irradiated young recipient mice. In this Opinion article, we make the case that the reliance on this approach has led to inaccurate conclusions regarding the effects of ageing on blood-forming stem cells; we suggest instead that changes in the environment contribute to haematopoietic system ageing. We propose that a complete understanding of how ageing affects haematopoiesis depends on the analysis of blood cell production in unperturbed mice. We describe how this can be achieved using in situ fate mapping. This approach indicates that changes in downstream progenitors, in addition to any HSC defects, may explain the reduced lymphopoiesis and sustained myelopoiesis that occur during ageing.

中文翻译:

造血干细胞会衰老吗?

人们认为,造血干细胞(HSC)中积累的遗传缺陷是造血功能与年龄相关的变化的原因,其中包括淋巴细胞减少和偏向髓系。这种以HSC为中心的观点主要基于研究,这些研究表明,成年小鼠的HSC在移植到受辐照的年轻受体小鼠后会表现出这些谱系偏倚。在本《意见》文章中,我们证明了对这种方法的依赖导致关于衰老对造血干细胞的影响的不正确结论。我们建议,环境的变化有助于造血系统的衰老。我们建议对衰老如何影响造血功能的完整理解取决于对未受干扰的小鼠血细胞产生的分析。我们描述了如何使用原位命运映射来实现这一点。这种方法表明,除任何HSC缺陷外,下游祖细胞的变化可能解释了衰老过程中淋巴细胞生成减少和持续的骨髓生成减少。
更新日期:2019-11-18
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