Circadian variations in clock gene expression of human bone marrow CD34+ cells.
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.
Tsinkalovsky
Oleg
O
Stem Cell Research Group, the Gade Institute, Department of Pathology, Haukeland University Hosptial, Bergen, Norway.
Smaaland
Rune
R
Rosenlund
Benedikte
B
Sothern
Robert B
RB
Hirt
Asle
A
Steine
Solrun
S
Badiee
Azadeh
A
Abrahamsen
Jenny Foss
JF
Eiken
Hans Geir
HG
Laerum
Ole Didrik
OD
D056930:ARNTL Transcription Factors; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis*; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics; D001854:Bone Marrow Cells / Q000502:physiology*; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002940:Circadian Rhythm / Q000502:physiology*; D056931:Cryptochromes; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005420:Flavoproteins / Q000096:biosynthesis* / Q000235:genetics; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics; D013739:Testosterone / Q000097:blood; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D056930:ARNTL Transcription Factors; D018952:Antigens, CD34; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D004268:DNA-Binding Proteins; D005420:Flavoproteins; D019382:Human Growth Hormone; D006854:Hydrocortisone; D009687:Nuclear Proteins; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013739:Testosterone; D015534:Trans-Activators; D014157:Transcription Factors; C538960:BMAL1 protein, human; C538961:Bmal1 protein, mouse; C064353:NR1D1 protein, human; C539022:PER1 protein, human; C421902:PER2 protein, human; C539023:Per1 protein, mouse; C538943:CLOCK protein, human; C538944:Clock protein, mouse