HIGH RESOLUTION MAPPING OF PLACENTAL GENE EXPRESSION

胎盘基因表达的高分辨率图谱

• 批准号: 6911379
• 负责人: JEFFREY O PENTECOST
• 金额: $ 14.35万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6911379
• 关键词: cell type; clinical research; computer simulation; gene expression; genetic markers; human pregnant subject; immunocytochemistry; in situ hybridization; model design /development; morphometry; photomicrography; placenta; prenatal growth disorder

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.

描述（由申请人提供）：有充分证据表明，成人心血管疾病源于胎儿发育期间的母体/胎盘生理条件。Barker（1990）证实，婴儿时期胎盘较大的成年人患高血压的风险较高。Lesage et al（2002）表明，子宫胎盘功能障碍导致的胎儿生长受限导致成人心血管疾病和糖尿病风险增加。宫内生长受限（IUGR）和低出生体重（LBW）的病因与母体营养不良有关（Bajoria，2002，Greenwood，2003，Fall，2003）。胎盘功能不全是IUGR和LBW病因学的核心，IUGR和LBW使个体易患冠心病、糖尿病、高血压和中风{Anthony，2003 2271 /id}。在胎盘疾病状态下，胎盘终末绒毛发生改变（Biagini，1989 - 1656，Mayhew，2003）。为了推进预防和干预措施，我们必须了解所有基因表达程序的适应性和适应不良的胎盘生理。分析胎盘相关的基因组，蛋白质组学和形态学数据集的新方法是必要的。需要在全面的解剖学背景下可视化多个基因标记以将基因表达与表型相关联的工具。我们建议生产的方法可视化胎盘基因表达idata在高分辨率的3D图形模型的终端绒毛。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3D计算机原型的终端绒毛及其组成组织类型的基因表达数据可以映射。具体目标：1。修订标记胎盘终末绒毛组织类型的方法; 2.生成3D规范模型，描述具有细胞级分辨率的绒毛结构，以包括所有细胞类型。该目标包括组织分割和绒毛形态的3D标准化。3.开发一种将基因表达数据与3D典型胎盘模型相结合的计算方法。