title: The protective role of symmetric stem cell division on the accumulation of heritable damage.
abstract: Stem cell divisions are either asymmetric-in which one daughter cell remains a stem cell and one does not-or symmetric, in which both daughter cells adopt the same fate, either stem or non-stem. Recent studies show that in many tissues operating under homeostatic conditions stem cell division patterns are strongly biased toward the symmetric outcome, raising the question of whether symmetry confers some benefit. Here, we show that symmetry, via extinction of damaged stem-cell clones, reduces the lifetime risk of accumulating phenotypically silent heritable damage (mutations or aberrant epigenetic changes) in individual stem cells. This effect is greatest in rapidly cycling tissues subject to accelerating rates of damage accumulation over time, a scenario that describes the progression of many cancers. A decrease in the rate of cellular damage accumulation may be an important factor favoring symmetric patterns of stem cell division.
authors.affiliation: Center for Complex Biological Systems & Department of Cell and Developmental Biology, University of California Irvine, Irvine, California, United States of America.
authors.forename: Peter T
authors.initials: PT
authors.lastname: McHale
authors.affiliation: Center for Complex Biological Systems & Department of Cell and Developmental Biology, University of California Irvine, Irvine, California, United States of America.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Lander
mesh_terms: D000818:Animals; D002455:Cell Division / Q000235:genetics*; D017491:Genes, APC; D042822:Genomic Instability; D007421:Intestine, Small / Q000166:cytology; D051379:Mice; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D013234:Stem Cells