ONE of the hottest races in biology, the hunt for the chemicals that reset a cell鈥檚 identity, just got hotter. Researchers have discovered that frog eggs seem to make the nucleus of an adult human cell revert to a state like that of an embryonic stem cell.
Since frog eggs are easy to obtain and work with, the finding should give the search for these mystery molecules a huge boost. And if they can be identified and exploited, the possibilities are immense. Doctors, for example, might be able to take any kind of cell from a patient and transform it into the type needed to treat them.
As a cell develops, chemical markers are added to its DNA, permanently switching some genes on and others off. A skin cell, for instance, has a very different genetic program from a muscle cell. But when the nucleus of an adult cell is placed inside an egg during cloning, some factor or factors inside the egg reset the cell鈥檚 program to an embryonic state, allowing it to develop into any cell type.
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Biologists have so far failed to identify these factors. 鈥淵ou can鈥檛 do it with mammalian eggs,鈥� says stem-cell researcher Rudolph Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. Mouse and human eggs are very small, he says, so searching for reprogramming molecules in them has been difficult. Human eggs are also in very short supply.
John Gurdon of the Wellcome Trust/Cancer Research UK Institute in Cambridge turned to frog eggs instead. His team injected adult mouse and human cells into the nucleus of frog eggs. In both types of cells, the gene Oct-4 was turned on, which is widely regarded as the best marker for an embryonic stem-cell state. 鈥淭hat tells you the mechanisms of nuclear reprogramming are conserved from frogs to humans,鈥� says cloning expert Jose Cibelli of Michigan State University in East Lansing.
The level of Oct-4 expression in the human cells was as great as in embryonic stem cells. At the same time, genes indicative of an adult cell were turned off, as if the cell had begun to reverse its identity (Current Biology, vol 13, p 1206).
Without more experiments we won鈥檛 know for sure that the adult nuclei are truly reversing their fate. But if they are, frog eggs could be the key to studying reprogramming. A single frog has about 20,000 eggs, which are 4000 times the size of their mammalian counterparts. 鈥淭he frog oocyte is really a huge supply of reprogramming agent,鈥� says Gurdon. Researchers could screen chemicals inside the eggs to identify the elusive factors. Once the key molecules are identified, he says, finding the human equivalents should be easy.
An advantage of this method is that human cells inserted into frog eggs do not divide, so there should be no risk of creating human embryos. So the key early events in cloning could be studied without cloning taking place 鈥� a useful option in countries such as the US where cloning research is restricted. Reprogramming adult cells could also yield 鈥渆mbryonic stem cells鈥� without having to destroy a human embryo.