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...

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