Four-gene cocktail for stem cells

Adult skin cells can be converted into embryonic-like stem cells by the addition of a cocktail of just four genes, two papers published today reveal.

Two teams, one from Japan and led by Shinya Yamanaka of Kyoto University, and the other from the US, led by James Thomson of the University of Madison, have independently shown that the insertion of four genes can reprogram adult fibroblasts into so-called induced pluripotent stem cells (iPSs).

The induced pluripotent cells are similar but not identical to embryonic stem cells, the researchers say.

Last year, Yamanaka showed that four genes encoding transcription factors - OCT3, SOX2, c-MYC and KLF4 - could transform mouse tail cells into iPSs. (See Graeme O'Neill's story, Stem cells: back to the future, for more information.)

The team has now shown that, surprisingly, the same four transcription factors can reprogram adult fibroblasts into the pluripotent stem cells.

Yamanaka's paper is published online today in Cell.

"From about 50,000 transfected human cells, we obtained approximately 10 iPS cell clones," Yamanaka said in a statement.

"This efficiency may sound very low, but it means that from one experiment, with a single 10cm dish, you can get multiple iPS cell lines."

The iPS cells were indistinguishable from embryonic stem cells in terms of their appearance and behaviour in cell culture, the researchers say.

Thomson's team used a similar method but with two different genes. In its paper in Science, Thomson's team identified, like Yamanaka, OCT3 and SOX2, but also two different genes - NANOG and LIN28.

This team used cells from foetal skin and the foreskin of a newborn baby and were able to transform about one in 10,000 cells. Yamanaka's team used cells from the facial skin of an adult woman and connective tissue from an adult man.

"We should now be able to generate patient- and disease-specific iPS cells, and then make various cells, such as cardiac cells, liver cells and neural cells," Yamanaka said.

"These cells should be extremely useful in understanding disease mechanisms and screening effective and safe drugs.

"If we can overcome safety issues, we may be able to use human iPS cells in cell transplantation therapies."