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

Yu Hou, Wen Li, Yue Sheng, Liping Li, Yong Huang, Zhonghui Zhang, Tongyu Zhu, David Peace, John G. Quigley, Wenshu Wu, You Yang Zhao, Zhijian Qian*

*Corresponding author for this work

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)810-818
Number of pages9
JournalNature Immunology
Volume16
Issue number8
DOIs
StatePublished - Jul 21 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Hou, Y., Li, W., Sheng, Y., Li, L., Huang, Y., Zhang, Z., Zhu, T., Peace, D., Quigley, J. G., Wu, W., Zhao, Y. Y., & Qian, Z. (2015). The transcription factor Foxm1 is essential for the quiescence and maintenance of hematopoietic stem cells. Nature Immunology, 16(8), 810-818. https://doi.org/10.1038/ni.3204