Intermittent Stem Cell Cycling Balances Self-Renewal and Senescence of the C. elegans Germ Line
| Autor: | Adrian Paz, Michael Chiang, Sam Hallman, Indre Vysniauskaite, Oliver Yuan, Charless C. Fowlkes, Olivier Cinquin, Amanda Cinquin |
|---|---|
| Přispěvatelé: | Kim, Stuart K |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Aging M Phase Cell Cycle Checkpoints Nematoda DNA Repair Physiology Apoptosis Regenerative Medicine Germline Animal Cells Replication Protein A Medicine and Health Sciences Reproductive system Cell Cycle and Cell Division Cell Self Renewal Genetics (clinical) Cellular Senescence Ecology Reproduction Stem Cells Animal Models Cell biology DNA-Binding Proteins Cell Processes OVA Stem Cell Research - Nonembryonic - Non-Human Female Stem cell Anatomy Cellular Types Cell aging Genital Anatomy Research Article Senescence Cell Physiology Cell Cycling lcsh:QH426-470 1.1 Normal biological development and functioning Biology Research and Analysis Methods 03 medical and health sciences Model Organisms Underpinning research Genetics Animals Gonads Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Ecology Evolution Behavior and Systematics Ovary Reproductive System Organisms Biology and Life Sciences Cell Biology Stem Cell Research Sperm Invertebrates lcsh:Genetics 030104 developmental biology Germ Cells Starvation Caenorhabditis Oocytes Physiological Processes Organism Development Developmental Biology DNA Damage Transcription Factors |
| Zdroj: | PLoS Genetics, Vol 12, Iss 4, p e1005985 (2016) PLoS Genetics Cinquin, A; Chiang, M; Paz, A; Hallman, S; Yuan, O; Vysniauskaite, I; et al.(2016). Intermittent Stem Cell Cycling Balances Self-Renewal and Senescence of the C-elegans Germ Line. PLOS GENETICS, 12(4), e1005985. doi: 10.1371/journal.pgen.1005985. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/0z8679t5 PLoS genetics, vol 12, iss 4 |
| ISSN: | 1553-7404 1553-7390 |
| DOI: | 10.1371/journal.pgen.1005985. |
| Popis: | Self-renewing organs often experience a decline in function in the course of aging. It is unclear whether chronological age or external factors control this decline, or whether it is driven by stem cell self-renewal—for example, because cycling cells exhaust their replicative capacity and become senescent. Here we assay the relationship between stem cell cycling and senescence in the Caenorhabditis elegans reproductive system, defining this senescence as the progressive decline in “reproductive capacity,” i.e. in the number of progeny that can be produced until cessation of reproduction. We show that stem cell cycling diminishes remaining reproductive capacity, at least in part through the DNA damage response. Paradoxically, gonads kept under conditions that preclude reproduction keep cycling and producing cells that undergo apoptosis or are laid as unfertilized gametes, thus squandering reproductive capacity. We show that continued activity is in fact beneficial inasmuch as gonads that are active when reproduction is initiated have more sustained early progeny production. Intriguingly, continued cycling is intermittent—gonads switch between active and dormant states—and in all likelihood stochastic. Other organs face tradeoffs whereby stem cell cycling has the beneficial effect of providing freshly-differentiated cells and the detrimental effect of increasing the likelihood of cancer or senescence; stochastic stem cell cycling may allow for a subset of cells to preserve proliferative potential in old age, which may implement a strategy to deal with uncertainty as to the total amount of proliferation to be undergone over an organism’s lifespan. Author Summary Stem cell cycling is expected to be beneficial because it helps delay aging, by ensuring organ self-renewal. Yet stem cell cycling is best used sparingly: cycling likely causes mutation accumulation—increasing the likelihood of cancer—and may eventually cause stem cells to senesce and thus stop contributing to organ self renewal. It is unknown how self-renewing organs make tradeoffs between benefits and drawbacks of stem cell cycling. Here we use the C. elegans reproductive system as a model organ. We characterize benefits and drawbacks of stem cell cycling—which are keeping worms primed for reproduction, and reducing the number of future progeny worms may bear, respectively. We show that, under specific conditions of reproductive inactivity, stem cells switch back and forth between active and dormant states; the timing of these switches, whose genetic control we start delineating, appears random. This randomness may help explain why populations of aging, reproductively-inactive worms experience an increase in the variability of their reproductive capacity. Stochastic stem cell cycling may underlie tradeoffs between self-renewal and senescence in other organs. |
| Databáze: | OpenAIRE |
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