title: Control of Caenorhabditis elegans germ-line stem-cell cycling speed meets requirements of design to minimize mutation accumulation.
abstract: BACKGROUND
  Stem cells are thought to play a critical role in minimizing the accumulation of mutations, but it is not clear which strategies they follow to fulfill that performance objective. Slow cycling of stem cells provides a simple strategy that can minimize cell pedigree depth and thereby minimize the accumulation of replication-dependent mutations. Although the power of this strategy was recognized early on, a quantitative assessment of whether and how it is employed by biological systems is missing.
  
  
  RESULTS
  Here we address this problem using a simple self-renewing organ - the C. elegans gonad - whose overall organization is shared with many self-renewing organs. Computational simulations of mutation accumulation characterize a tradeoff between fast development and low mutation accumulation, and show that slow-cycling stem cells allow for an advantageous compromise to be reached. This compromise is such that worm germ-line stem cells should cycle more slowly than their differentiating counterparts, but only by a modest amount. Experimental measurements of cell cycle lengths derived using a new, quantitative technique are consistent with these predictions.
  
  
  CONCLUSIONS
  Our findings shed light both on design principles that underlie the role of stem cells in delaying aging and on evolutionary forces that shape stem-cell gene regulatory networks.
authors.affiliation: Department of Developmental & Cell Biology, University of California, Irvine, California, USA.|Center for Complex Biological Systems, University of California, Irvine, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Chiang
authors.affiliation: Department of Developmental & Cell Biology, University of California, Irvine, California, USA.|Center for Complex Biological Systems, University of California, Irvine, California, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Cinquin
authors.affiliation: Department of Developmental & Cell Biology, University of California, Irvine, California, USA.|Center for Complex Biological Systems, University of California, Irvine, California, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Paz
authors.affiliation: University of Amsterdam, Institute for Informatics, Amsterdam, Netherlands.
authors.forename: Edward
authors.initials: E
authors.lastname: Meeds
authors.affiliation: Department of Developmental & Cell Biology, University of California, Irvine, California, USA.|Center for Complex Biological Systems, University of California, Irvine, California, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Price
authors.affiliation: University of Amsterdam, Institute for Informatics, Amsterdam, Netherlands.|Donald Bren School of Information and Computer Sciences, University of California, Irvine, California, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Welling
authors.affiliation: Department of Developmental & Cell Biology, University of California, Irvine, California, USA. ocinquin@uci.edu.|Center for Complex Biological Systems, University of California, Irvine, California, USA. ocinquin@uci.edu.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cinquin
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D053263:Gene Regulatory Networks; D005854:Germ Cells / Q000166:cytology*; D000067552:Mutation Accumulation; D015398:Signal Transduction / Q000235:genetics