Reprogrammed by a frog

Dolly, Polly, and friends proved that somatic cells are potentially totipotent, but the reprogramming that a somatic cell nucleus must undergo during cloning remains an error-prone black box. James Byrne, John Gurdon, and colleagues (University of Cambridge, UK) have now shown that the biochemically tractable frog oocyte system can be used to model reprogramming. A modified version of their protocol might allow the isolation of elusive reprogramming factors and, eventually, the reprogramming of somatic human cells for self-transplantation of stem cells.

The Cambridge group chose frog oocytes because, unlike most eggs, oocytes are not at all active in replication but very strongly so in transcription. To see if this transcriptional activity extended to reprogramming, Gurdon microinjected the oocytes with various cells: first mouse fetal fibroblasts, then mouse adult thymic cells, and finally human lymphocytes. All cell types eventually showed robust expression of oct4, whose expression is specific to and preserves the fate of stem cells.

Transcriptional activity not associated with stem cells, such as that of β-actin and the thymus marker thy-1, was reduced or extinguished by the transfer. But the extent of the transformation is not yet clear. “It's possible that what we are doing is turning everything into an oocyte,” says Gurdon. But he believes that oct4 expression is a good sign that the cells are at least headed toward becoming stem cells.

Stem cell characteristics may develop only through sequential inductive events. But the optimists are hoping that there is a single extract that will do the entire conversion. The success of the current experiments, says Gurdon, is “one of the more compelling reasons for believing that to be true.” ▪

Reference: