One of the biggest holy grails in biology involves finding a means to generate pluripotent and infinitely replicating stem cells without generating an embryo. One Japanese team presented some potent clues last night at the Keystone conference on stem cell biology -- but stem cell researchers will need a few more bread crumbs before they can put this potentially exciting information to use.

Shinya Yamanaka from Kyoto University and the Japan Science and Technology Agency presented a series of experiments designed to identify key reprogramming factors that convert a somatic cell into an embryonic one. Starting from a list of 100 proto-oncogenes and embryonic stem (ES) cell associated transcripts, or ECATs, he and his co-author winnowed the list to 24, then 10, then 4; all, when combined, appeared to induce pluripotency in murine embryonic MEF cells. (Below four factors, the authors were unable to obtain seemingly viable colonies.) The four factors also successfully reprogrammed fibroblasts from adult mice, and the authors plan to continue their work in human fibroblasts.

This all sounded very exciting, until Yamanaka concluded his talk without naming the four seemingly crucial factors for reprogramming a somatic cell. A series of probing questions from the audience revealed a few details -- most are likely present in the oocyte, and may change the length of the cell cycle. He admitted that one factor is Oct4, which plays an important role in the maintenance of pluripotency, and is a key actor in much of the research presented during the conference. "I?m not brave enough to tell the other three," Yamanaka concluded.