Stem cell chronicles: autobiographies within genomes.

Human stem cell studies are difficult because many of the powerful experimental approaches that mark and follow stem cells and their progeny are impractical. Moreover, humans are long-lived, and it would literally take a lifetime to follow stem cell fates prospectively. Considering these hurdles, an ideal method would not require prior experimental manipulations but still allow "observations" of human stem cells from birth to death. The purpose of this review is to outline how histories or fates are likely to be surreptitiously recorded within somatic cell genomes by replication errors (molecular clock hypothesis). It may be possible to reconstruct stem cell lifetimes by measuring the random somatic changes that accumulate within their genomes, or the genomes of their more-easy-to-identify progeny.