title: Clock gene Bmal1 is dispensable for intrinsic properties of murine hematopoietic stem cells.
abstract: BACKGROUND
  Circadian rhythms are known to influence a variety of biological phenomena such as cell cycle, sleep-wake rhythm, hormone release and other important physiological functions. Given that cell cycle entry of hibernating hematopoietic stem cells (HSCs) plays a critical role in controlling hematopoiesis, we asked functional significance of the clock gene Bmal1, which plays a central role in regulating circadian rhythms as a transcription factor. Here we investigated the necessity of Bmal1 for HSC functions using Bmal1 deficient (Bmal1⁻/⁻) mice.
  
  
  RESULTS
  Using colony-forming assays in vitro, we found that the frequency of mixed colony formation between Bmal1⁺/⁺ and Bmal1⁻/⁻ CD34-KSL cells does not differ significantly. Competitive bone marrow assays also revealed that Bmal1⁻/⁻ bone marrow cells competed normally with wild-type cells and displayed long-term multi-hematopoietic lineage reconstitution. In addition, there were no significant differences in the frequencies and hibernation state of bone marrow HSCs between Bmal1⁺/⁺ and Bmal1⁻/⁻ mice, suggesting that they are independent of circadian rhythms.
  
  
  CONCLUSIONS
  This paper discusses the necessity of circadian rhythms for HSC functions. Our data clearly shows that a key circadian clock gene Bmal1 is dispensable for intrinsic functions of HSCs, such as differentiation, proliferation and repopulating ability.
authors.forename: Aki
authors.initials: A
authors.lastname: Ieyasu
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tajima
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shimba
authors.affiliation: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, the Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan. nakauchi@ims.u-tokyo.ac.jp.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamazaki
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002940:Circadian Rhythm; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse