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© The Rockefeller University Press, 0021-9525/2003/6/1008 $5.00
The Journal of Cell Biology, Volume 161, Number 6, 1008-1008

A tumorigenic culprit in ES cells

Cells expressing ERas form tumors in mice. Yamanaka/Macmillan

In the debate over whether ES cells or somatic stem cells have better prospects for stem cell therapies, ES cell proponents admit that their pluripotent cells carry an increased risk: ES cells can form teratomas. But now Kazutoshi Takahashi, Kaoru Mitsui, and Shinya Yamanaka (Nara Institute of Science and Technology, Nara, Japan) have found that a newly discovered Ras gene may be at the heart of this problem.

ERas, previously thought to be a pseudogene, was found by the group as being expressed specifically in ES cells. The other genes in this expression class are also expressed in early embryonic tissues such as the inner cell mass and epiblast, but no expression of ERas is evident in the embryo. The lack of phenotype of ERas knockout mice adds to the mystery.

Yamanaka suggests that ERas may be connected to the LIF/Stat3 pathway, which is dispensable for normal mouse development but necessary in ES cells and for the extended survival of mouse blastocysts (a process called diapause). Only in the ES cells and during diapause must pluripotency be extended past a few days, and this extension may be helped by LIF or ERas expression. The situation is clouded further in humans and monkeys, however, as both have apparently functional ERas genes but lack diapause.

Whatever the function of ERas, "ERas null cells should be much safer for clinical applications," says Yamanaka. ERas has residues characteristic of activated Ras proteins, and is found largely in the activated, GTP-bound form. Its addition transforms cells, whereas its deletion from ES cells sharply reduces their tumor-forming ability. Growth is also reduced in ERas knockout cells, but Yamanaka says that rich culture conditions largely correct for this and thus slow growth should not hold back the use of altered ES cells. Direct human applications will not, however, come from Yamanaka's group in the foreseeable future, as there are extensive bureaucratic hurdles involved in experimentation on human ES cells in Japan.

Reference:

Takahashi, K., et al. 2003. Nature. 423:541–545.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 722K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?