杭州师范大学的研究团队在四月十六日的Nature Communications杂志上发表文章，揭示了造血干细胞衰老的一个重要机制。

野生型p53诱导磷酸酶1(Wip1)负调节几种肿瘤抑制基因和DNA损伤反应通路。然而,Wip1影响造血干细胞(HSC)体内平衡和衰老仍然未知。我们的研究表明,Wip1高度表达在肝星状细胞,但随着年龄的增长而减少。

    研究显示，Wip1缺陷型小鼠在多个层面上表现出造血干细胞的衰老，比如HSC池增大，再生活性受损。去除p53可以挽救Wip1−/−造血干细胞的再生缺陷，同时不影响细胞衰老或凋亡。这说明Wip1–p53通路能够调控造血干细胞的分化，而且不依赖传统的p53通路。

不过，去除p53不会影响Wip1缺陷型小鼠HSC池的大小。进一步研究表明，Wip1缺陷型小鼠的HSC池扩大是由mTORC1介导的。这项研究为人们展示了一个重要的干细胞衰老机制，p53和mTORC1通路对造血干细胞衰老的不同影响受到Wip1的控制。

    原文链接：Wip1 deficiency impairs haematopoietic stem cell function via p53 and mTORC1 pathways

    原文摘要：Wild-type p53-induced phosphatase 1 (Wip1) negatively regulates several tumour suppressor and DNA damage response pathways. However, the impact of Wip1 on haematopoietic stem cell (HSC) homeostasis and aging remains unknown. Here we show that Wip1 is highly expressed in HSCs but decreases with age. Wip1-deficient (Wip1−/−) mice exhibited multifaceted HSC aging phenotypes, including the increased pool size and impaired repopulating activity. Deletion of p53 rescued the multilineage repopulation defect of Wip1−/− HSCs without affecting cellular senescence or apoptosis, indicating that the Wip1–p53 axis regulates HSC differentiation in a manner independent of conventional p53 pathways. However, p53 deletion did not influence the increased HSC pool size in Wip1−/− mice. Interestingly, the expansion of HSCs in Wip1−/− mice was due to an mTORC1-mediated HSC proliferation. Thus, our study reveals a mechanism of stem cell aging, in which distinct effects of p53 and mTORC1 pathways on HSC aging are governed by Wip1.