GENOME-WIDE IDENTIFICATION OF GENES REQUIRED FOR DECIDUALIZATION

蜕化所需基因的全基因组鉴定

• 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
• 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

 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（由申请人提供）：人类不育是一个全球性问题，胚胎植入失败占自然妊娠和体外受精过程中妊娠失败的很大比例。着床是一个极其复杂的过程，需要精确控制激素、生长因子信号和细胞-细胞接触，以协调有能力的囊胚和接受子宫之间的相互作用。蜕膜化是着床过程的一部分，包括成纤维细胞样子宫内膜间质细胞的快速增殖，然后分化为上皮样蜕膜细胞，后者后来成为围绕着床孕体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，早期蜕膜化缺陷也可导致其他妊娠缺陷，如胎盘形成、胎儿宫内生长和分娩。由于缺乏合适的高通量筛选工具，迄今为止尚未对蜕膜化过程进行系统的研究。在这里，我们描述了这样一个体外筛选工具，包含一个荧光读出蜕膜化的一代。在目的I中，我们将使用这种体外筛选工具进行全基因组shRNA筛选，以确定新的蜕膜化基因。在目的II中，我们将分析蜕膜化所需的转录因子的时间诱导，并建立一个导致蜕膜化的转录因子网络。该项目的成功完成将对多个研究领域产生长期影响，包括植入生物学，避孕，体外受精和环境毒理学。