Identification of Cell-Specific Transcriptional Programs that Drive Cervical Remo
识别驱动宫颈 Remo 的细胞特异性转录程序
基本信息
- 批准号:10602527
- 负责人:
- 金额:$ 7.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:3-Dimensional37 weeks gestationATAC-seqAutomobile DrivingBirthCell Culture SystemCell NucleusCell modelCell physiologyCellsCervicalCervix UteriChromatinCollagen FiberCollagen FibrilCollecting CellCompetenceComplexCuesDataData SetDefectDepositionDeveloped CountriesDevelopmentDiscipline of obstetricsEarly identificationElastic FiberEnhancersEstrogensEtiologyEventExtracellular MatrixExtracellular Matrix ProteinsFetusFiberFoundationsFunctional disorderFutureGene ExpressionGene TargetingGenesGeneticGenetic TranscriptionGenomicsGoalsHormonalHormonesHumanIncidenceIndividualInfantK-Series Research Career ProgramsKnockout MiceKnowledgeMechanicsMediatingMediatorModificationMolecularMorbidity - disease rateMusNewborn InfantOutcomePathway interactionsPerinatal mortality demographicsPhasePhenotypePopulationPredictive FactorPregnancyPregnancy ComplicationsPregnancy MaintenancePremature BirthPreparationPreventionProcessProgesteroneProteinsRegulator GenesRegulatory PathwayResearch PersonnelResolutionRiskRisk FactorsRoleSignal TransductionSolidStromal CellsStructureSystemTechnologyTestingTimeTissuesUnited StatesValidationWild Type Mousebiomarker identificationcell typecervical remodelingclinically relevantconditional knockoutdecorinearly pregnancygene networkgene regulatory networkin vivoinnovationmolecular dynamicsmouse modelneonatenovelperinatal morbiditypost-doctoral trainingpregnantpreservationprogramspromoterreproductiveresiliencesingle-cell RNA sequencingsteroid hormonetherapeutic targettranscription factortranslational impact
项目摘要
Premature Birth (PTB) is the most common complication during pregnancy leading to a high incidence of perinatal morbidity and mortality rates in developed countries. According to the CDC, in 2018, 1 of every 10 newborns delivered preterm in the United States. An understanding of the molecular processes that determine a successful pregnancy and on time parturition is essential in order to elucidate the diverse mechanisms by which this process can go awry and lead to a premature birth. The transformation of the cervix from a closed rigid structure to one that can open sufficiently for passage of a term infant is one such process. The significance of the proposed studies is the potential to advance understanding of the dynamic molecular events that regulate cervical remodeling at the cellular level. The focus of this application is to utilize innovative single cell genomic technologies that will allow us to define gene regulatory networks that drive cervical remodeling. We will identify regions of active transcription at single cell resolution in the mouse cervix from nonpregnant, time points in pregnancy, and in labor. Utilizing novel computational approaches previously used to study cellular reprogramming events in development, this data will be used to understand how each cell type transitions its phenotype to implement the dynamic process of remodeling and identify the cell specific transcription factors that drive these cell specific molecular changes. Functional validation of the identified transcription factors will be carried out using a human 3D-cervical cell culture system and studies in normal mice and mouse models with targeted deletion of the transcription factors. The proposed studies will provide a solid and broad foundation of understanding of cellular events that drive cervical remodeling which will allow the discovery of risk factors for premature birth that are not yet known and will uncover new pathways to explore for therapeutic targets for prevention of preterm birth. In addition, these studies will provide me the scientific and technical knowledge required for a successful postdoctoral training and importantly, will set the foundation to apply for K awards aiding in my transition to becoming an independent investigator in the reproductive field.
早产(PTB)是妊娠期最常见的并发症,导致发达国家围产期发病率和死亡率很高。根据CDC的数据,2018年,美国每10个新生儿中就有1个早产。了解决定成功怀孕和按时分娩的分子过程是至关重要的,以便阐明这一过程可能出错并导致早产的各种机制。子宫颈从一个封闭的刚性结构转变为一个可以充分打开以供足月婴儿通过的结构就是这样一个过程。拟议的研究的意义是潜在的推进了解的动态分子事件,调节宫颈重塑在细胞水平上。该应用的重点是利用创新的单细胞基因组技术,使我们能够定义驱动宫颈重塑的基因调控网络。我们将确定在单细胞分辨率在小鼠子宫颈从非怀孕,在怀孕的时间点,并在劳动的转录活跃的地区。利用以前用于研究发育中细胞重编程事件的新计算方法,这些数据将用于了解每种细胞类型如何转变其表型以实现重塑的动态过程,并确定驱动这些细胞特异性分子变化的细胞特异性转录因子。将使用人3D宫颈细胞培养系统和正常小鼠和靶向缺失转录因子的小鼠模型中的研究对所鉴定的转录因子进行功能验证。拟议的研究将为理解推动宫颈重塑的细胞事件提供坚实而广泛的基础,这将允许发现尚不清楚的早产风险因素,并将发现探索预防早产治疗靶点的新途径。此外,这些研究将为我提供成功的博士后培训所需的科学和技术知识,重要的是,将为申请K奖奠定基础,帮助我过渡到成为生殖领域的独立研究者。
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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Mariano Colon-Caraballo其他文献
Mariano Colon-Caraballo的其他文献
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{{ truncateString('Mariano Colon-Caraballo', 18)}}的其他基金
Identification of Cell-Specific Transcriptional Programs that Drive Cervical Remo
识别驱动宫颈 Remo 的细胞特异性转录程序
- 批准号:
10407489 - 财政年份:2021
- 资助金额:
$ 7.84万 - 项目类别:
Identification of Cell-Specific Transcriptional Programs that Drive Cervical Remo
识别驱动宫颈 Remo 的细胞特异性转录程序
- 批准号:
10231426 - 财政年份:2021
- 资助金额:
$ 7.84万 - 项目类别: