Genome-wide microarray evidence that 8-cell human blastomeres over-express cell cycle drivers and under-express checkpoints

June, 2010: The second report by Bedford scientists about cell division appeared, as the cover story of the JOURNAL OF ASSISTED REPRODUCTION AND GENETICS. The work builds on the previous report of CLOCK genes that indicate early stem cells may be under the control of circadian rhythms (see report at bedfordresearch.org). These novel findings about controls on cell multiplication will be used in the derivation of parthenogenic stem cells to attempt to improve the efficiency and stability of new stem cell lines.

Abstract

Purpose To understand cell cycle controls in the 8-Cell human blastomere. Methods Data from whole human genome (43,377 elements) microarray analyses of RNAs from normal 8-Cell human embryos were compiled with published microarrays of RNAs from human fibroblasts, before and after induced pluripotency, and embryonic stem cells. A sub database of 3,803 genes identified by high throughput RNA knock-down studies, plus genes that oscillate in human cells, was analyzed. Results Thirty-five genes over-detected at least 7-fold specifically on the 8-Cell arrays were enriched for cell cycle drivers and for proteins that stabilize chromosome cohesion and spindle attachment and limit DNA and centrosome replication to once per cycle.

Conclusions These results indicate that 8-cell human blastomere cleavage is guided by cyclic over-expression of key proteins, rather than canonical checkpoints, leading to rapidly increasing gene copy number and a susceptibility to chromosome and cytokinesis mishaps, well-noted characteristics of preimplantation human embryos.

Keywords Aurora kinase . Cell cycle . CLOCK . Cyclins . Human embryo . RB