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遗传方法，以研究基因在正常和疾病状态下血液发育中的调节和作用。通过使用复杂的基因工程策略，可以以多种方式改变小鼠胚胎干细胞（ES）中的基因（以使其重复或修改其功能或表达）。小鼠ES具有无限细胞分裂和分化成几乎所有细胞类型的能力，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，用于研究任何遗传改变在细胞和生理水平上的影响。该计划的一个主要重点是通过将人类DNA序列的大区域引入小鼠ES细胞来建立更准确的人类血液疾病模型。这些人类DNA序列可以被改变以重现已知的人类疾病相关突变，因此可以创建用于评估人类疾病病理学和潜在药物疗法的实验动物模型。此外，一个平行的方法是应用遗传工程策略，以人类胚胎干细胞。遗传改变的人ES细胞可以在培养皿中分化以产生血细胞，因此允许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

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

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

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