title: 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.
authors.affiliation: Department of Medicine and Cancer Research Center, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Medicine and Cancer Research Center, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Medicine and Cancer Research Center, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: 1] Department of Medicine and Cancer Research Center, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA. [2] Fudan University ZhongShan Hospital, Shanghai, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.affiliation: Section of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Medicine and Cancer Research Center, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA.
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Fudan University ZhongShan Hospital, Shanghai, China.
authors.forename: Tongyu
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Medicine and Cancer Research Center, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA.
authors.forename: David
authors.initials: D
authors.lastname: Peace
authors.affiliation: Department of Medicine and Cancer Research Center, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Quigley
authors.affiliation: Department of Medicine and Cancer Research Center, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA.
authors.forename: Wenshu
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Pharmocology, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA.
authors.forename: You-Yang
authors.initials: YY
authors.lastname: Zhao
authors.affiliation: Department of Medicine and Cancer Research Center, The University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Qian
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D005434:Flow Cytometry; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C491524:Foxm1 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2