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Journal of Biological Rhythms
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Circadian Variations in Clock Gene Expression of Human Bone Marrow CD34+ Cells

Oleg Tsinkalovsky

Stem Cell Research Group, the Gade Institute, Department of Pathology, Haukeland University Hosptial, Bergen, Norway, ole.larum{at}gades.uib.no.

Rune Smaaland

Department of Medicine, Haukeland University Hospital, Bergen, Norway

Benedikte Rosenlund

Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

Robert B. Sothern

The Rhythmometry Laboratory, College of Biological Sciences, Biological Sciences Center, University of Minnesota, St. Paul

Asle Hirt

Department of Cardiology, Haukeland University Hospital, Bergen, Norway

Solrun Steine

Stem Cell Research Group, the Gade Institute, Department of Pathology, Haukeland University Hosptial, Bergen, Norway

Azadeh Badiee

Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

Jenny Foss Abrahamsen

Department of Medicine, Haukeland University Hospital, Bergen, Norway

Hans Geir Eiken

Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

Ole Didrik Laerum

Stem Cell Research Group, the Gade Institute, Department of Pathology, Haukeland University Hosptial, Bergen, Norway

Time-dependent variations in clock gene expression have recently been observed in mouse hematopoietic cells, but the activity of these genes in human bone marrow (BM) has so far not been investigated. Since such data can be of considerable clinical interest for monitoring the dynamics in stem/progenitor cells, the authors have studied mRNA expression of the clock genes hPer1 , hPer2, hCry1, hCry2, hBmal1, hRev-erb {alpha}, and hClock in human hematopoietic CD34-positive (CD34 +) cells. CD34+ cells were isolated from the BM samples obtained from 10 healthy men at 6 times over 24 h. In addition, clock gene mRNA expression was analyzed in the whole BM in 3 subjects. Rhythms in serum cortisol, growth hormone, testosterone, and leukocyte counts documented that subjects exhibited standardized circadian patterns. All 7 clock genes were expressed both in CD34+ cells and the whole BM, with some differences in magnitude between the 2 cell populations. A clear circadian rhythm was shown for hPer1, hPer2, and hCry2 expression in CD34+ cells and for hPer1 in the whole BM, with maxima from early morning to midday. Similar to mouse hematopoietic cells, h Bmal1 was not oscillating rhythmically. The study demonstrates that clock gene expression in human BM stem/progenitor cells may be developmentally regulated, with strong or weaker circadian profiles as compared to those reported in other mature tissues.

Key Words: hematopoiesis • clock genes • stem cells • human bone marrow • circadian rhythm

Journal of Biological Rhythms, Vol. 22, No. 2, 140-150 (2007)
DOI: 10.1177/0748730406299078


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