Differentiated cells may hold more promise than adult stem cells.
Surely it's easier to clone mammals from cells that are dividing, than from those fated never to do so again? That's certainly the assumption with which most biologists have been working.
But results from a study in mice suggest that the opposite may be true: in attempts to clone mouse embryos from three groups of blood cells, the most differentiated ones worked best. The finding could improve the lamentable state of cloning, although experts are stumped for an explanation.
In cloning, researchers insert the nucleus of a cell, say a skin cell, into an egg stripped of its own nucleus. This process is thought to reprogramme the DNA in the nucleus, giving it the potential to orchestrate the development of an embryo. Nuclei from stem cells, which can give rise to various other types of cells, were assumed to be easier to reprogramme than nuclei from differentiated cells that have lost the ability to divide. Cloning from embryonic stem cells is much more successful than from adult stem cells, for example.
Now Jerry Yang of the University of Connecticut, Storrs, and his colleagues have compared mouse blood cells at three stages of differentiation. One group comprised stem cells that could produce all blood-cell types. A second group of cells could make only a handful of cell types, and a third group was composed of completely differentiated white blood cells called granulocytes.
The granulocytes were easiest to clone. With these cells, 35% of cloning attempts yielded young embryos, compared with 11% in the intermediate group and less than 8% from the stem cells (L.-Y. Sung et al. Nature Genet. doi:10.1038/ng1895; 2006).
Scientists have long debated whether cloning is so difficult because reprogramming doesn't work well, or because the few clones produced grew from rare stem cells lurking among the differentiated cells used. Dolly the sheep, hailed as the first mammal cloned from an adult cell, was created from a mammary gland — but some claim she could have come from a stem cell in that tissue.
Previous attempts to clone from fully differentiated cells have been problematic, and it's possible that granulocytes may simply contain particular biochemical factors that make them easy to clone. But if Yang's result holds generally, Dolly may have come from a differentiated cell after all. It would also be good news for the technique of therapeutic cloning, in which researchers hope to clone patients' cells and use the resulting embryos to extract embryonic stem cells to treat disease.