GENOME-WIDE IDENTIFICATION OF GENES REQUIRED FOR DECIDUALIZATION

蜕化所需基因的全基因组鉴定

基本信息

批准号：
9258455
负责人：
Liang Ma
金额：
$ 19.06万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-08 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9258455
关键词：
Biology Birth Cell Line Cells Cherry - dietary Clone Cells Conceptus Contraceptive methods Decidual Cell Decidual Cell Reactions Defect Endometrial Stromal Cell Event Factor Analysis Failure Fertilization in Vitro Fetal Growth Fibroblasts Generations Genes Genetic Growth Factor Harvest Hormonal Human Implant In Vitro Infertility Lead Libraries Pathway interactions Placentation Polyploidy Pregnancy Procedures Process Prolactin Proteins Reporter Reproduction Research Signal Transduction Stromal Cells Time Tissues Uterus blastocyst deep sequencing environmental chemical environmental toxicology failure Implantation genome-wide genome-wide analysis high throughput screening human embryonic stem cell implantation natural Blastocyst Implantation novel promoter public health relevance red fluorescent protein response screening small hairpin RNA tool transcription factor

Biology Birth Cell Line Cells Cherry - dietary Clone Cells Conceptus Contraceptive methods Decidual Cell Decidual Cell Reactions Defect Endometrial Stromal Cell Event Factor Analysis Failure Fertilization in Vitro Fetal Growth Fibroblasts Generations Genes Genetic Growth Factor Harvest Hormonal Human Implant In Vitro Infertility Lead Libraries Pathway interactions Placentation Polyploidy Pregnancy Procedures Process Prolactin Proteins Reporter Reproduction Research Signal Transduction Stromal Cells Time Tissues Uterus blastocyst deep sequencing environmental chemical environmental toxicology failure Implantation genome-wide genome-wide analysis high throughput screening human embryonic stem cell implantation natural Blastocyst Implantation novel promoter public health relevance red fluorescent protein response screening small hairpin RNA tool transcription factor

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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. Here we describe the generation of such an in vitro screening tool that contains a fluorescent readout for decidualization. In Aim I we will use this in vitro screening tool to perform a genome-wide shRNA screen to identify novel genes for decidualization. In Aim II, we will analyze the temporal induction of transcription factors required for decidualization and establish a transcription factor network leading to 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（由应用提供）：人类不育症是一个全球问题，胚胎植入的失败占自然怀孕和体外受精程序期间妊娠失败的很大一部分。植入是一个极其复杂的过程，需要精确控制的激素，生长因子信号传导和细胞 - 细胞接触，该过程协调了主管胚泡和相关子宫之间的相互作用。固定化是植入过程的一部分，涉及快速的增殖，然后将成纤维细胞样子宫基质细胞分化为上皮样细胞，后来成为植入概念的决定组织的一部分。义词化缺陷可以直接导致植入失败。此外，早期的决定性缺陷也可能导致其他妊娠缺陷，例如胎盘，胎儿内胎儿生长和分娩。到目前为止，由于缺乏合适的高吞吐量筛选工具，因此尚未系统地研究决策过程。在这里，我们描述了这种体外筛选工具的产生，该工具包含用于决策的荧光读数。在目的中，我将使用此体外筛查工具来执行全基因组shRNA筛选，以鉴定新的基因进行决策。在AIM II中，我们将分析决策所需的转录因子的临时诱导，并建立转录因子网络导致决策。该项目的成功完成将对多个研究领域产生持久影响，包括植入生物学，避孕，体外受精和环境毒理学。