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

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.

SUBMITTER: Hou Y 

PROVIDER: S-EPMC4509925 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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

Hou Yu Y   Hou Yu Y   Li Wen W   Sheng Yue Y   Li Liping L   Huang Yong Y   Zhang Zhonghui Z   Zhu Tongyu T   Peace David D   Quigley John G JG   Wu Wenshu W   Zhao You-Yang YY   Qian Zhijian Z  

Nature immunology 20150629 8

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 th  ...[more]

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