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论文题目
Loss of Nupr1 promotes engraftment by tuning the quiescence threshold of hematopoietic stem cells via regulation of the p53-checkpoint pathway
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作者
Tongjie Wang,Chengxiang Xia,Qitong Weng, Kaitao Wang,Yong Dong,Sha Hao,Fang Dong,Xiaofei Liu,Lijuan Liu,Yang Geng,Yuxian Guan,Juan Du,Tao Cheng,Hui Cheng and Jinyong Wang
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论文出处
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刊物名称
Haematologica
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年卷期页
2022, 107, 1, 154-166
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联系作者
Jinyong Wang
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影响因子
8.039
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摘要
Hematopoietic stem cells (HSCs) are dominantly quiescent under homeostasis, which is a key mechanism of maintaining the HSC pool for life-long hematopoiesis. Dormant HSCs poise to be immediately activated on urgent conditions and can return to quiescence after regaining homeostasis. To date, the molecular networks of regulating the threshold of HSC dormancy, if exist, remain largely unknown. Here, we unveiled that deletion of Nupr1, a gene preferentially expressed in HSCs, activated the quiescence HSCs under homeostatic status, which conferred engraftment competitive advantage on HSCs without compromising their stemness and multi-lineage differentiation abilities in serial transplantation settings. Following an expansion protocol, the Nupr1-/- HSCs proliferate more robustly than their wild type counterparts in vitro. Nupr1 inhibits the expression of p53 and the rescue of which offsets the engraftment advantage. Our data unveil the de novo role of Nupr1 as an HSC quiescence-regulator, which provides insights into accelerating the engraftment efficacy of HSC transplantation by targeting the HSC quiescence-controlling network.
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英文摘要
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外单位作者单位
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备注
