Single cell analysis of the evolving mutational landscape in carcinogen exposed skin
对暴露于致癌物的皮肤中不断演变的突变景观的单细胞分析
基本信息
- 批准号:10038763
- 负责人:
- 金额:$ 9.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-11 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAutomobile DrivingBiological AssayBiological ModelsCancer BurdenCarcinogen exposureCarcinogensCell CompartmentationCellsChemical AgentsChemical ExposureClonal ExpansionDNA Sequence AlterationDNA sequencingDevelopmentDorsalEarly DiagnosisEpithelialEpitheliumExposure toFoundationsGeneticGenetic AnticipationHomeostasisIndividualInjuryIntestinesKnowledgeLungMalignant NeoplasmsMusMutateMutationNormal tissue morphologyPatternPopulationSkinSystemTimeTissuescarcinogenicityenvironmental chemicalhuman tissuein vivoregenerativesequencing platformsingle cell analysissingle cell sequencingstem cell populationstem cellstissue repairtumortumorigenesis
项目摘要
Abstract
The development of early detection approaches is fundamental to reduce the growing cancer
burden. Cellular accumulation of genetic mutations is believed to be the foundation of tumor
development, however, there is a fundamental lack of knowledge regarding the earliest stages of
tumorigenesis and whether certain cell populations may be more predisposed to acquire initial
driving mutations. Stem cells are long-lived cells which reside in tissues and serve as a
regenerative pool that actively maintain normal homeostasis and can repair tissue after injury.
Accumulating evidence indicates that stem cells may also serve as the cells of origin for
tumorigenesis in certain tissues and generate clonal expansions of mutated cells which could be
more susceptible to further genetic insults over time. As it is not feasible to address the evolving
mutational burden of stem cells in tissues of human individuals, this study will exploit mouse dorsal
skin, a highly informative regenerative model system with well characterized and distinct stem cell
populations. The dynamic mutation co-occurrence profiles of specific skin mouse stem cell
populations will be determined following exposure to known carcinogens utilizing a customizable,
single cell DNA-sequencing platform. This approach will identify whether certain mutational
profiles are selectively enriched and tolerated in specific stem cell populations over long periods
of time in functionally normal tissue following carcinogen exposure. The approach used by this
study could easily be adapted to screen many different chemical exposures and has the potential
to detect the earliest signs of cancer in similar epithelial tissue systems with shared stem cell
populations such as the lung and intestine – which are often exposed to long term environmental
and chemical insult - before tumors are evident and determine distinct carcinogen-exposure
signatures in cells.
摘要
项目成果
期刊论文数量(0)
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Eve Kandyba其他文献
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{{ truncateString('Eve Kandyba', 18)}}的其他基金
Single cell analysis of the evolving mutational landscape in carcinogen exposed skin
对暴露于致癌物的皮肤中不断演变的突变景观的单细胞分析
- 批准号:
10674848 - 财政年份:2020
- 资助金额:
$ 9.72万 - 项目类别:
Single cell analysis of the evolving mutational landscape in carcinogen exposed skin
对暴露于致癌物的皮肤中不断演变的突变景观的单细胞分析
- 批准号:
10461785 - 财政年份:2020
- 资助金额:
$ 9.72万 - 项目类别:
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