Resource for innovation and application of genetic engineering strategies in embryonic stem cells

胚胎干细胞基因工程策略的创新和应用资源

• 批准号: MC_UU_00016/10
• 负责人: Andrew Smith
• 金额: $ 149.21万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Intramural
• 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=MC_UU_00016%2F10
• 关键词: Resource; innovation; application; genetic; engineering

The aim of this research programme is to innovate experimental genetic approaches to investigate the regulation and role of genes in blood development in both normal and diseased states. By using sophisticated genetic engineering strategies genes can be altered in numerous ways (to inactivate them or modify their function or expression) in mouse embryonic stem (ES) cells. Mouse ES have the capacity for both unlimited cell division and differentiation into almost all cell types, and can create an entire organism. These cells therefore provide an experimental system for studying the effect of any genetic alterations both at cellular and physiological levels. A major focus of the programme is to build more accurate models of human blood diseases by introducing large regions of human DNA sequence into mouse ES cells. These human DNA sequences can be altered to recapitulate known human disease-associated mutations and thus it is possible to create an experimental animal model for evaluating human disease pathology and potential drug therapies. In addition, a parallel approach is being followed applying genetic engineering strategies to human ES cells. Genetically altered human ES cells can be differentiated in the culture dish to generate blood cells and therefore allow the effects of genetic alterations to be studied and evaluated.

该研究计划的目的是创新实验性遗传方法，以调查基因在正常状态和患病状态下基因在血液发育中的作用。通过使用复杂的基因工程策略，基因可以通过多种方式（使其失活或改变其功能或表达）在小鼠胚胎（ES）细胞中进行改变。小鼠ES具有无限细胞分裂的能力，几乎可以分化为所有细胞类型，并且可以创建整个生物体。因此，这些细胞提供了一个实验系统，用于研究细胞和生理水平上任何遗传改变的影响。该程序的主要重点是通过将大型人DNA序列引入小鼠ES细胞中来建立更准确的人类血液疾病模型。可以改变这些人DNA序列以概括已知的人类疾病相关突变，因此可以创建一个实验性动物模型，以评估人类疾病病理学和潜在的药物疗法。此外，正在采用一种平行的方法，将基因工程策略应用于人类ES细胞。遗传改变的人ES细胞可以在培养皿中分化以产生血细胞，因此可以研究和评估遗传改变的影响。

项目成果

On-microscope staging of live cells reveals changes in the dynamics of transcriptional bursting during differentiation

活细胞的显微镜分期揭示了分化过程中转录爆发动力学的变化

• DOI: 10.1101/2021.11.26.470114
• 发表时间: 2021
• 作者: Jeziorska D

Introducing Point Mutations into Human Pluripotent Stem Cells using Seamless Genome Editing.

使用无缝基因组编辑将点突变引入人类多能干细胞。

• DOI: 10.3791/61152
• 发表时间: 2020
• 期刊: JoVE
• 作者: Wang Y

Identification and Single-Cell Functional Characterization of an Endodermally Biased Pluripotent Substate in Human Embryonic Stem Cells.

• DOI: 10.1016/j.stemcr.2018.04.015
• 发表时间: 2018-06-05
• 期刊: Stem cell reports
• 影响因子: 5.9
• 作者: Allison TF;Smith AJH;Anastassiadis K;Sloane-Stanley J;Biga V;Stavish D;Hackland J;Sabri S;Langerman J;Jones M;Plath K;Coca D;Barbaric I;Gokhale P;Andrews PW
• 通讯作者: Andrews PW

On-microscope staging of live cells reveals changes in the dynamics of transcriptional bursting during differentiation.

• DOI: 10.1038/s41467-022-33977-4
• 发表时间: 2022-11-04
• 期刊: Nature communications
• 影响因子: 16.6