The transcription factor Foxm1 is essential for the quiescence and maintenance of hematopoietic stem cells

被引:73
作者
Hou, Yu [1 ,2 ]
Li, Wen [1 ,2 ]
Sheng, Yue [1 ,2 ]
Li, Liping [1 ,2 ,3 ]
Huang, Yong [4 ]
Zhang, Zhonghui [1 ,2 ]
Zhu, Tongyu [3 ]
Peace, David [1 ,2 ]
Quigley, John G. [1 ,2 ]
Wu, Wenshu [1 ,2 ]
Zhao, You-yang [5 ]
Qian, Zhijian [1 ,2 ]
机构
[1] Univ Illinois Hosp & Hlth Sci Syst, Dept Med, Chicago, IL 60612 USA
[2] Univ Illinois Hosp & Hlth Sci Syst, Canc Res Ctr, Chicago, IL USA
[3] Fudan Univ, ZhongShan Hosp, Shanghai 200433, Peoples R China
[4] Univ Chicago, Dept Med, Gastroenterol Sect, Chicago, IL 60637 USA
[5] Univ Illinois Hosp & Hlth Sci Syst, Dept Pharmacol, Chicago, IL USA
基金
美国国家卫生研究院;
关键词
SELF-RENEWAL; ENDOTHELIAL-CELLS; GENE-EXPRESSION; MOUSE MODELS; PROLIFERATION; MICE; TRANSPLANTATION; PROGRESSION; PROGENITOR; SURVIVAL;
D O I
10.1038/ni.3204
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Foxm1 is known as a typical proliferation-associated transcription factor. Here we found that Foxm1 was essential for maintenance of the quiescence and self-renewal capacity of hematopoietic stem cells (HSCs) in vivo in mice. Reducing expression of FOXM1 also decreased the quiescence of human CD34(+) HSCs and progenitor cells, and its downregulation was associated with a subset of myelodysplastic syndrome (MDS). Mechanistically, Foxm1 directly bound to the promoter region of the gene encoding the receptor Nurr1 (Nr4a2; called 'Nurr1' here), inducing transcription, while forced expression of Nurr1 reversed the loss of quiescence observed in Foxm1-deficient cells in vivo. Thus, our studies reveal a previously unrecognized role for Foxm1 as a critical regulator of the quiescence and self-renewal of HSCs mediated at least in part by control of Nurr1 expression.
引用
收藏
页码:810 / +
页数:11
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