Evidence that human blastomere cleavage is under unique cell cycle control.
OBJECTIVE
To understand the molecular pathways that control early human embryo development.


METHODS
Improved methods of linear amplification of mRNAs and whole human genome microarray analyses were utilized to characterize gene expression in normal appearing 8-Cell human embryos, in comparison with published microarrays of human fibroblasts and pluripotent stem cells.


RESULTS
Many genes involved in circadian rhythm and cell division were over-expressed in the 8-Cells. The cell cycle checkpoints, RB and WEE1, were silent on the 8-Cell arrays, whereas the recently described tumor suppressor, UHRF2, was up-regulated >10-fold, and the proto-oncogene, MYC, and the core element of circadian rhythm, CLOCK, were elevated up to >50-fold on the 8-Cell arrays.


CONCLUSIONS
The canonical G1 and G2 cell cycle checkpoints are not active in totipotent human blastomeres, perhaps replaced by UHRF2, MYC, and intracellular circadian pathways, which may play important roles in early human development.
Kiessling
Ann A
AA
Department of Obstetrics and Gynecology, Athens Medical School, Alexandra Maternity Hospital, Athens, Greece. kiessling@bedfordresearch.org
Bletsa
Ritsa
R
Desmarais
Bryan
B
Mara
Christina
C
Kallianidis
Kostas
K
Loutradis
Dimitris
D
D001757:Blastomeres / Q000502:physiology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002940:Circadian Rhythm; D004261:DNA Replication; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000378:metabolism*
D018797:Cell Cycle Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger