HIGH RESOLUTION MAPPING OF PLACENTAL GENE EXPRESSION

描述(由申请人提供)：有充分的证据表明成人心血管疾病源于胎儿发育过程中的母体/胎盘生理状况。Barker(1990)发现，胎盘较大的婴儿患高血压的风险较高。Lesage等人(2002)表明，子宫胎盘功能障碍导致的胎儿生长受限会增加成人患心血管疾病和糖尿病的风险。胎儿宫内生长受限(IUGR)和低出生体重(LBW)的病因与母亲营养不良有关(Bajoria，2002，Greenwood，2003，Fall，2003)。胎盘功能不全是IUGR和LBW的主要病因，这两种疾病易导致冠心病、糖尿病、高血压和中风[Anthony，2003 2271/id]。胎盘疾病状态下胎盘末端绒毛发生改变(Biagini，，1656，Mayhew，2003)。为了推进预防性和干预性实践，我们必须了解管理适应性和非适应性胎盘生理学的所有基因表达程序。需要新的方法来分析胎盘相关的基因组、蛋白质组和形态数据集。需要在一个全面的解剖学背景下可视化多个基因标记的工具，以将基因表达与表型相关联。我们提出了在末端绒毛的高分辨率3D图形模型中可视化胎盘基因表达IDATA的方法。基于组织学、免疫组织化学和原位杂交信息，我们将产生一个末端绒毛及其组成组织类型的3D计算机原型，基因表达数据可以在其上绘制。具体目标：1.修订胎盘末端绒毛组织类型的标记方法；2.生成描述绒毛结构的3D规范模型，细胞级分辨率包括所有细胞类型。这一目标包括组织分割和绒毛形态的3D标准化。3.提出了一种将基因表达数据与三维标准胎盘模型相结合的计算方法。

DESCRIPTION (provided by applicant): There is ample showing adult cardiovascular disease takes root from maternal/placental physiologic conditions during fetal development. Barker (1990) demonstrated higher risk of hypertension in adults who had been small babies with large placentas. Lesage et al (2002) showed that fetal growth restriction from uteroplacental dysfunction causes increased risk for cardiovascular disease and diabetes in adults. The etiology of intrauterine growth restriction (IUGR) and low birth weight (LBW) relates to maternal undernutrition (Bajoria, 2002, Greenwood, 2003, Fall, 2003). Placental insufficiency is central to the etiology of IUGR and LBW which predispose individuals to coronary heart disease, diabetes, hypertension and stroke {Anthony, 2003 2271 /id}. The placental terminal villi are altered in placental disease states (Biagini, 1989 1656, Mayhew, 2003). To advance preventative and interventional practices, we must understand all gene expression programs governing adaptive and maladaptive placental physiology. New methods for analyzing placenta-related genomic, proteomic, and morphological datasets are needed. Tools for visualizing multiple gene markers within a comprehensive anatomical context to correlate gene expression with phenotype are needed. We propose to produce methods for visualizing placental gene expression idata in high-resolution 3D graphical models of terminal villi. Based on histological, immunohistochemical, and in situ hybridization information we will produce a 3D computer prototype of a terminal villus and its constituent tissue types upon which gene expression data can be mapped. Specific Aims: 1. Revise methodologies for labeling placental terminal villus tissue types; 2. Generate 3D canonical models describing villous architecture with cell-level resolution to include all cell-types. This aim includes segmentation of tissues and 3D standardization of villous morphology. 3. Develop a computational approach for combining gene expression data with 3D canonical placenta models.