Expression of the transcription factor Oct4, a marker of pluripotency, is a necessary prerequisite for development of both normal and cloned embryos. In the July 15 Current Biology, James Byrne and colleagues at the Wellcome Trust/Cancer Research UK Institute of Cancer and Developmental Biology report the expression of Oct4 during reprogramming of transferred differentiated nuclei into Xenopus oocytes. Their results indicate a repression of expression of differentiation markers and a rapid and strong induction of the Oct4 transcription factor (Current Biology, 13:1206-1213, July 15, 2003).

Byrne et al. transferred nuclei from about 100 fully differentiated mouse thymocytes into the germinal vesicles of Xenopus oocytes and monitored Oct4 expression by reverse transcription polymerase chain reaction (RT-PCR) during incubation of the oocytes. They observed fully spliced transcripts as early as 2 days after incubation at 18°C—the equivalent of 12 hours at 37°C—and also after 5.5, 7, and 9 days. Quantitative RT-PCR revealed levels of expression equivalent to those found in pluripotent mouse embryonic stem cells. Their investigation of Oct4 expression in transferred human adult lymphocytes yielded similar results. They confirmed the species specificity of the Oct4 transcripts and ruled out the possibility that the transcripts were due to stress effects in the Xenopus oocytes. In addition, no incompatibility was seen between mammalian nuclei and amphibian oocytes. DNA synthesis and replication were not required for Oct4 gene expression, thus disproving the hypothesis that DNA replication is central to the process of Xenopus oocyte transcriptional reprogramming.

"We believe that the ability of amphibian oocyte components to induce stem cell gene expression in normal mouse and human adult somatic cells, and the abundant availability of amphibian oocytes, encourages the long-term hope that it may eventually be possible to directly reprogram cells, easily obtained from adult human patients, to a stem cell condition," conclude the authors.