Frog eggs rejuvenate human cells

Amphibian extract may take adult DNA back to stem-cell state.
15 July 2003

HELEN R. PILCHER
Frog eggs: useful for finding the genes involved in cell reprogramming.
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Immature frog eggs can rejuvenate adult human cells. Molecules in the amphibian nucleus coax mature human and mouse DNA back to an adaptable, stem-cell-like state1.

John Gurdon and his colleagues at Cambridge University, UK, hope to isolate the substances responsible and use them to reprogramme ordinary adult cells, from skin or blood, say. This would yield a limitless supply of donor-matched stem cells with which to repair tissue damaged in diseases such as Parkinson's and multiple sclerosis.

Many researchers are hoping to convert specialized adult cells into a more immature state. Stem cells can be derived from excess early-stage human embryos from fertility treatments. But this approach has ethical and practical limitations - the European Union last week ruled that only embryos created before 27 June 2002 can be used for research. Adult stem cells exist, but their potential is uncertain.

Gurdon's team injected immature Xenopus frog eggs with nuclei from adult mouse or human white blood cells. Two days later, the definitive mouse or human stem-cell marker, a molecule called Oct4 RNA, appeared in the hybrid. RNA helps to convert DNA to proteins, so the result hints that the adult nuclei are starting to behave in a stem-cell-like way.

"This is the first step in reprogramming cells," agrees developmental geneticist Wolf Reik of the Babraham Institute in Cambridge, UK, before adding: "You might still run into problems later on." Some genes may remain in their adult form, causing cells to divide and become cancerous.

Nuclear reaction

The technique is different from the process used to create Dolly the sheep. To make Dolly, researchers injected adult DNA into an empty sheep egg and stimulated it to develop. Gurdon's approach leaves the egg's nucleus in place.

When the researchers injected the adult nuclei into frog egg nucleii, rather than into the surrounding cytoplasm, Oct4 levels shot up by a factor of ten.

"The reprogramming activity is particularly concentrated here," says Gurdon.
Molecules in the frog nucleus may be responsible for the eggs' revitalizing abilities, he speculates.

Frog eggs are large and easy to manipulate, says cell biologist Rudolf Jaenisch of the Whitehead Institute in Cambridge, Massachusetts. "They give you a useful tool for finding the genes that are involved in reprogramming," he says.

References
1. Byrne, J. A., Simonsson, S., Western, P. S. & Gurdon, J. B. Nuclei of adult mammalian somatic cells are directly reprogrammed to oct-4 stem cells gene expression by amphibian oocytes. Current Biology, 13, 1206 - 1213, (2003).

http://www.nature.com/nsu/030714/030714-3.html