Understanding early envirnomental influences on human epigenetic programmes

了解早期环境对人类表观遗传程序的影响

• 批准号: 2585683
• 金额: --
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2585683
• 关键词: Understanding; early; envirnomental; influences; human

Previous work has focused on identifying loci whose methylation state varies between individuals but shows strong cross-tissue correlation within individuals, suggestive that the methylation marks were established in the pregastrulation embryo. These regions, recognised as sensitive to periconceptional environment- based on seasonality in Gambian cohorts- are enriched for metastable epialleles and regions of parent-of-origin methylation, many of which demark imprinted loci solely in the placenta. In order to understand the mechanisms involved in variation at these environmentally sensitive methylation hotspots, it is crucial to dissect the methylation profiles of different cells within our model tissue; the placenta. The project will involve generating global expression and methylation profiles in placenta samples from the Gambia collected across consecutive rainy-dry seasons and correlating outcomes with prenatal exposures. Once established, nutrition exposures associated with between individual methylation differences will be modelled using a placenta organoid system.

以前的工作集中在识别基因座，其甲基化状态在个体之间变化，但在个体内显示出很强的跨组织相关性，这表明甲基化标记是在原肠胚形成前胚胎中建立的。这些地区，被认为是敏感的围受孕环境-在冈比亚队列的季节性的基础上-是丰富的亚稳态表观等位基因和区域的父母的起源甲基化，其中许多区分印记位点仅在胎盘。为了了解这些环境敏感的甲基化热点的变异机制，解剖我们的模型组织（胎盘）中不同细胞的甲基化谱至关重要。该项目将涉及在冈比亚连续多雨-干旱季节收集的胎盘样本中生成全球表达和甲基化谱，并将结果与产前暴露相关联。一旦建立，将使用胎盘类器官系统对与个体间甲基化差异相关的营养暴露进行建模。