Author:
Wang Tongjie,Xia Chengxiang,Weng Qitong,Wang Kaitao,Dong Yong,Hao Sha,Dong Fang,Liu Xiaofei,Liu Lijuan,Geng Yang,Guan Yuxian,Du Juan,Cheng Tao,Cheng Hui,Wang Jinyong
Abstract
Hematopoietic stem cells (HSC) are dominantly quiescent under homeostasis, which is a key mechanism of maintaining the HSC pool for life-long hematopoiesis. Dormant HSC are poised to be immediately activated in certain conditions and can return to quiescence after homeostasis has been regained. At present, the molecular networks of regulating the threshold of HSC dormancy, if existing, remain largely unknown. Here, we show that deletion of Nupr1, a gene preferentially expressed in HSC, activated quiescent HSC under homeostasis, which conferred a competitive engraftment advantage for these HSC without compromising their stemness or multi-lineage differentiation capacity in serial transplantation settings. Following an expansion protocol, the Nupr1-/- HSC proliferated more robustly than their wild-type counterparts in vitro. Nupr1 inhibits the expression of p53 and rescue of this inhibition offsets the engraftment advantage. Our data reveal a new role for Nupr1 as a regulator of HSC quiescence, which provides insights for accelerating the engraftment efficacy of HSC transplantation by targeting the HSC quiescence-controlling network.
Publisher
Ferrata Storti Foundation (Haematologica)
Cited by
10 articles.
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