AN IN VITRO SCREENING TOOL FOR DECIDUALIZATION
一种用于分化的体外筛选工具
基本信息
- 批准号:8969886
- 负责人:
- 金额:$ 19.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-08-03 至 2017-07-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingBiologyBirthCell LineCellsChemicalsClinicClinicalClustered Regularly Interspaced Short Palindromic RepeatsCollectionConceptusContraceptive AgentsContraceptive methodsDecidual CellDecidual Cell ReactionsDecidual ReactionDefectDevelopmentEndocrine disruptionEndometrial Stromal CellFDA approvedFailureFertility AgentsFertilization in VitroFetal GrowthFibroblastsFoundationsGenesGenomicsGrowth FactorHormonalHumanIGFBP1 geneImplantIn VitroInfertilityLeadLibrariesModificationPharmaceutical PreparationsPlacentationPlayPolyploidyPreclinical Drug EvaluationPregnancyProceduresProcessReporterReproductionResearchRoleTechnologyTissuesUterusblastocystdrug developmentenvironmental chemicalenvironmental toxicologyfailure Implantationgenome editinghigh throughput screeninghuman embryonic stem cellimplantationintercellular communicationnatural Blastocyst Implantationnovelpublic health relevancereproductiveresearch studyscreeningsmall molecule librariestool
项目摘要
DESCRIPTION (provided by applicant): Human infertility is a global problem and failure of embryo implantation accounts for a significant percentage of pregnancy failure during both natural pregnancy and in vitro fertilization procedures. Implantation is an extremely complicated process requiring precisely controlled hormonal, growth factor signaling and cell-cell contacts which coordinate interactions between the competent blastocysts and the receptive uterus. Decidualization is part of the implantation process and involves rapid proliferation then differentiation of fibroblast-like endometrial stromal cells into epitheloid-like decidual cells whch later become part of the decidual tissue that surrounds the implanting conceptus. Decidualization defects can directly lead to implantation failure. In addition, early decidualizatin defects can also lead to other pregnancy defects such as placentation, intrauterine fetal growth, and parturition. Up to now, the process of decidualization has not been systematically studied due to the lack of a suitable high throughput screening tool. In this proposal, we propose to generate such much-needed tool using the recently developed state-of-the-art CRISPR/Cas genome editing technology. In Aim I we will use CRISPR to generate a dual-reporter cell line for decidualization by knocking two fluorescent reporters into endogenous loci of decidual markers. In Aim II, we will use this new tool to perform a small scale high throughput screening for chemical compounds that can interfere with decidualization. Successful completion of this project will have a long-lasting impact in multiple research fields including implantation biology,
contraception, in vitro fertilization and environmental toxicology. .
描述(由申请人提供):人类不孕症是一个全球性问题,在自然妊娠和体外受精过程中,胚胎植入失败占妊娠失败的很大一部分。植入是一个极其复杂的过程,需要精确控制激素、生长因子信号传导。协调感受态囊胚和接受子宫之间相互作用的细胞-细胞接触是植入过程的一部分,涉及快速增殖,然后分化为成纤维细胞样。子宫内膜基质细胞分化为上皮样蜕膜细胞,进而成为植入孕体周围的蜕膜组织的一部分。蜕膜化缺陷可直接导致着床失败。此外,早期蜕膜化缺陷还可导致其他妊娠缺陷,如胎盘形成、宫内缺陷等。迄今为止,由于缺乏合适的高通量筛选工具,尚未系统地研究蜕膜化过程。在该提案中,我们建议使用最近开发的最先进的 CRISPR/Cas 基因组编辑技术来生成急需的工具。在目标 I 中,我们将使用 CRISPR 通过敲除两个荧光来生成用于蜕膜化的双报告细胞系。在目标 II 中,我们将使用这种新工具对可能干扰蜕膜化的化合物进行小规模高通量筛选。多个研究领域,包括植入生物学、
避孕、体外受精和环境毒理学。
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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$ 19.06万 - 项目类别:
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