The protective role of symmetric stem cell division on the accumulation of heritable damage

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 patter...

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Bibliographic Details
Published in:PLoS computational biology 2014-08, Vol.10 (8), p.e1003802-e1003802
Main Authors: McHale, Peter T, Lander, Arthur D
Format: Article
Language:English
Subjects:
Animals
Biology and Life Sciences
Cancer
Cell division
Cell Division - genetics
Colon
Deoxyribonucleic acid
DNA
Epigenetic inheritance
Epigenetics
Genes, APC
Genetic aspects
Genetic research
Genomic Instability
Health aspects
Homeostasis
Intestine, Small - cytology
Mathematical models
Mice
Models, Genetic
Mutation
Mutation - genetics
Population
Renewals
Stem cell research
Stem Cells
Studies
Symmetry
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Summary: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.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1003802