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

Nature Immunology volume 16, pages 810818 (2015) | Download Citation

Abstract

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.

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Acknowledgements

We thank M.A. Goodell (Baylor College of Medicine) for the plasmid MSCV-FlagNurr1. Supported by the US National Institutes of Health (RO1 CA140979 to Z.Q.).

Author information

Affiliations

  1. Department of Medicine and Cancer Research Center, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA.

    • Yu Hou
    • , Wen Li
    • , Yue Sheng
    • , Liping Li
    • , Zhonghui Zhang
    • , David Peace
    • , John G Quigley
    • , Wenshu Wu
    •  & Zhijian Qian
  2. Fudan University ZhongShan Hospital, Shanghai, China.

    • Liping Li
    •  & Tongyu Zhu
  3. Section of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.

    • Yong Huang
  4. Department of Pharmocology, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA.

    • You-yang Zhao

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Contributions

Y.Ho., W.L., Y.S., L.L., Y.Hu. and Z.Z. performed research; T.Z., D.P., J.G.Q., W.W. and Y.Z. provided advice, reagents and/or analytic tools; Y.Ho. and Z.Q. designed the research and performed data analysis; and Y.Ho., D.P., J.G.Q. and Z.Q. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Zhijian Qian.

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https://doi.org/10.1038/ni.3204

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