Development of pluripotent cell lines from Livestock, and animal models for pharmacology/toxicology applications

开发来自牲畜的多能细胞系以及用于药理学/毒理学应用的动物模型

• 批准号: 1959635
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1959635
• 关键词: Development; pluripotent; cell; lines; Livestock

Reprogramming of cells to a pluripotent embryonic state through iPSC (induced pluripotent stem cell) based technologies has revolutionised prospects for the development of cellular therapies and drug development. Successful translation of these advances to animal research models and livestock has important applications in developing cell-based experimental platforms for studying the genetic and molecular basis of the healthy organism, production traits and disease resistance -as well as disease progression, intervention strategies, drug testing and toxicology. Unfortunately, until now reprogramming strategies for non-murine or human cells has met with limited success. However, very recent advances in understanding the requirements for reprogramming and the development of culture systems that promote the expansion of extended pluripotent stem cells have meant that generating and exploiting reprogrammed animal cells is now possible1-3. The overall aim of this project is to develop reprogrammed animal cells using these contemporary state-of-the-art methodologies, characterise their differentiation potential and investigate their utility. Initially the project will focus on novel iPSCs provided by Professor Pentao Liu at the Sanger Institute. These cells have been created using these novel technologies and have been made available for the project.The objectives of the project are:1. Evaluate the self-renewal properties of the extended pluripotent stem cells and translate this technology to the derivation of iPSCs from other species - including animals used in pharmacology/toxicology applications. This will test the hypothesis that these novel technologies are more effective for reprogramming and promoting propagation of stem cells from different species and contribute to understanding the regulation of cellular signalling mechanisms within these cells.2. Evaluate the differentiation potential of these novel pluripotent cells and determine if this can be manipulated through genetically modification. This will test the hypothesis that loss and gain of function experiments can direct the programming and expansion of specific progenitor cells from these novel cell lines. This will involve the use of CRISPR gene editing to generate lineage marked cells (e.g. muscle, gut, macrophage) to monitor differentiation.This project will complement the application of cell based systems for interrogating the wealth of genetic data from animal breeding experiments, as part of the Roslin Institutes new BBSRC Institute Strategic Programme, and will broaden the scope of the iPSC-related expertise at Censo biotechnologies.

通过基于iPSC（诱导多能干细胞）的技术将细胞重编程为多能胚胎状态已经彻底改变了细胞治疗和药物开发的发展前景。将这些进展成功地转化为动物研究模型和牲畜，在开发基于细胞的实验平台以研究健康生物体的遗传和分子基础、生产性状和抗病性以及疾病进展、干预策略、药物测试和毒理学方面具有重要应用。不幸的是，到目前为止，非小鼠或人类细胞的重编程策略取得了有限的成功。然而，最近在了解重编程的要求和培养系统的发展方面取得的进展，促进了扩展多能干细胞的扩展，这意味着产生和利用重编程的动物细胞现在是可能的1-3。该项目的总体目标是利用这些当代最先进的方法开发重新编程的动物细胞，表征它们的分化潜力并研究它们的效用。最初，该项目将专注于桑格研究所刘鹏涛教授提供的新型多能干细胞。这些细胞是使用这些新技术创建的，并已提供给该项目。该项目的目标是：1。评估扩展多能干细胞的自我更新特性，并将该技术转化为从其他物种（包括用于药理学/毒理学应用的动物）中衍生的iPSCs。这将验证这些新技术对不同物种干细胞的重编程和增殖更有效的假设，并有助于理解这些细胞内细胞信号机制的调节。评估这些新型多能细胞的分化潜力，并确定这是否可以通过基因改造来操纵。这将验证功能实验的损失和获得可以指导这些新细胞系中特定祖细胞的编程和扩增的假设。这将涉及使用CRISPR基因编辑来生成谱系标记细胞（例如肌肉、肠道、巨噬细胞）以监测分化。作为罗斯林研究所新的BBSRC研究所战略计划的一部分，该项目将补充基于细胞的系统的应用，用于查询动物育种实验中丰富的遗传数据，并将扩大Censo生物技术公司ipsc相关专业知识的范围。