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Control of Caenorhabditis elegans germ-line stem-cell cycling speed meets requirements of design to minimize mutation accumulation.
Chiang, Michael; Cinquin, Amanda; Paz, Adrian; Meeds, Edward; Price, Christopher A; Welling, Max; Cinquin, Olivier.
Afiliação
  • Chiang M; Department of Developmental & Cell Biology, University of California, Irvine, California, USA.
  • Cinquin A; Center for Complex Biological Systems, University of California, Irvine, California, USA.
  • Paz A; Department of Developmental & Cell Biology, University of California, Irvine, California, USA.
  • Meeds E; Center for Complex Biological Systems, University of California, Irvine, California, USA.
  • Price CA; Department of Developmental & Cell Biology, University of California, Irvine, California, USA.
  • Welling M; Center for Complex Biological Systems, University of California, Irvine, California, USA.
  • Cinquin O; University of Amsterdam, Institute for Informatics, Amsterdam, Netherlands.
BMC Biol ; 13: 51, 2015 Jul 18.
Article em En | MEDLINE | ID: mdl-26187634
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ciclo Celular / Caenorhabditis elegans / Acúmulo de Mutações / Células Germinativas Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: BMC Biol Assunto da revista: BIOLOGIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ciclo Celular / Caenorhabditis elegans / Acúmulo de Mutações / Células Germinativas Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: BMC Biol Assunto da revista: BIOLOGIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos