Jan. 13, 2003
By Ricki Lewis
The Scientist, Volume 17, Issue 1, 9
As researchers track the signals that lure stem cells along apparent developmental detours, it is beginning to look like the cells' plasticity is a natural response to injury. At first, the stem cells seemed to breach the boundaries set in the early embryo, morphing from mesoderm to endoderm, ectoderm to mesoderm, and variations on that theme. This transdifferentiation was originally thought to be a rarity, but cases have accumulated and a new view is emerging: What if everything can turn into everything?
Transdifferentiation is the culmination of a highly coordinated response to signals--involving sensing, trafficking, and sometimes cell fusion--that plays out against a backdrop of gene expression possibilities. "There are specific biological conditions under which stem cell plasticity occurs. We don't yet know the molecular cues, but we think that local tissue environment is key," says Richard Mulligan, professor of genetics at Harvard Medical School.
Mulligan's group recently identified 216 genes whose combined expression imparts a state of "stemness" (M. Ramalho-Santos et al., "'Stemness': transcriptional profiling of embryonic and adult stem cells," Science, 298:597-600, Oct. 18, 2002). Only four of the genes are uniquely used in stem cells; 35 take part in signaling; 100 are of unknown function. Integrins are particularly important, linking the extracellular matrix to signals entering and leaving cells. The cell switches seen so far may be the tip of an iceberg.
Because all cells contain all genes, anything is possible. "Stem cells are like minicomputers with all the software loaded, all the programs necessary to convert to any cell type. A stem cell should be able to do anything if we tell it the right set of signals," says Bryon Petersen, assistant professor of pathology at the University of Florida in Gainesville. And sorting out those signals, many stem cell biologists say, will be critical for regenerative medicine. The American Society for Cell Biology's Summer Meeting, to be held Aug. 9-12, 2003 at Montana State University in Bozeman, will address the coming crossroads of signal transduction and stem cell biology (www.ascb.org/news/vol25no11/ns/November-02.html).
© 2003, The Scientist Inc.