Progressive states of cell-cycle withdrawal
细胞周期退出的进行性状态
基本信息
- 批准号:10803979
- 负责人:
- 金额:$ 34.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-30 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AgeAgingAlgorithmsBiological MarkersBiologyCell AgingCell Culture TechniquesCell CycleCell Cycle ProgressionCell SeparationCell divisionCell physiologyCellsChronic DiseaseChronologyDNA DamageDevelopmentDiseaseDrug usageEventFlow CytometryFunctional disorderGenotoxic StressHealth Care CostsHumanKnowledgeLengthLightMalignant NeoplasmsMeasuresMedicalMicroscopyModelingModernizationMolecularMorbidity - disease rateNaturePathologyPharmaceutical PreparationsPhysiologicalPopulationProbabilityProcessProliferatingRegenerative capacityRejuvenationRelapseRestRoleSafetySomatic CellSortingTechnologyTestingTherapeuticWithdrawalWorkcancer therapycell agecell injurychemotherapeutic agentgenetic signaturegenotoxicityhuman diseasehuman old age (65+)improvedinflammatory milieumolecular markermortalitypredictive signaturepreventreproductivesenescencesensorsingle cell technologysingle-cell RNA sequencingtelomeretranscriptomicstumor
项目摘要
Project Summary
Senescence is the process by which a cell permanently stops proliferating due to cellular aging
or damage but does not die. Induction of senescence is often desirable during cancer treatment
to prevent the proliferation of aberrant cells, but it also impedes cellular function and
regenerative capacity as we age. The study of cellular senescence is hindered by the fact that
senescence is difficult to distinguish from other states of cell-cycle withdrawal such as
quiescence, a transient cellular resting state. This is because quiescence and senescence are
defined by overlapping molecular markers and because these cell-cycle transitions occur
heterogeneously from cell to cell. Despite obvious medical relevance, it is unclear whether
senescence and quiescence are truly distinct states. Here we propose to test the hypothesis
that senescence and quiescence exist on a continuum of cell-cycle withdrawal where the
probability of cell-cycle re-entry steadily declines toward zero as cells become senescent.
We will leverage our unique expertise in long-term, time-lapse microscopy, automated single-
cell tracking, and the development of sensors for cell-cycle progression and cell-cycle
withdrawal to unveil gradations of cell-cycle withdrawal that are invisible by standard bulk
approaches. Our specific aims are 1) To determine the predictive power of prevailing
senescence markers as binary markers of senescence and as graded markers of quiescence
depth, 2) To determine at the transcriptomic level whether quiescence and senescence are
distinct states or part of a continuum of cell-cycle withdrawal, and 3) To the identify the DNA
damage and telomere features that predict permanent cell-cycle withdrawal as cells age toward
replicative senescence.
If successful, this work will improve our ability to define molecularly the state of senescence and
will generate new fundamental knowledge about the onset of senescence. Our work could
improve the ability to predict tumor relapse after cancer therapy, help quantify a cell’s
physiological age and reproductive potential, identify ways to rejuvenate aged cells, and
improve the safety of senolytic drugs that eliminate senescent cells.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Sabrina Leigh Spencer其他文献
Sabrina Leigh Spencer的其他文献
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{{ truncateString('Sabrina Leigh Spencer', 18)}}的其他基金
Proliferation-quiescence control by integration of stress and mitogen signaling
通过整合应激和有丝分裂原信号传导来控制增殖-静止
- 批准号:
8766464 - 财政年份:2014
- 资助金额:
$ 34.96万 - 项目类别:
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