转录因子介导的心室肌细胞定向分化研究
结题报告
批准号:
31970680
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
金守光
依托单位:
学科分类:
细胞命运及重编程
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
金守光
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中文摘要
心血管疾病极大地威胁着人类的健康,由于成人心肌细胞缺乏自我更新能力,一旦受损会导致不可逆转的心脏功能衰竭。多能干细胞不单可体外扩增还可诱导分化为心肌细胞,是制备心肌细胞的理想来源。可是,从多能干细胞所分化出的心肌细胞往往是多种细胞亚型组成的混合物,不能直接用于细胞移植来治疗心肌梗死。上述混合物中,心室肌细胞是最具有应用价值的亚细胞型。然而,如何控制心肌细胞前体向心室肌细胞的定向分化乃是当前的技术难题。发育生物学研究结果显示转录因子NKX2.5、dHAND、HEY2、IRX4和Foxa2与心室肌细胞特异性分化相关。本项目将采用一种新型的蛋白质递送技术Bac-T3SS,在心肌细胞分化的不同阶段,将上述转录因子以蛋白质的形式导入细胞内,诱导心室肌细胞的定向分化和成熟。该方法具有安全性高、转录因子注入效率高、成本低等优点,适用于大规模生产,具有广泛应用前景。
英文摘要
Cardiovascular diseases impose grave threat to the human health. As adult cardiomyocytes lack self renewal capacity, heart tissue damage usually results in irreversible loss of function. Pluripotent stem cells (PSCs) can self renew while maintaining the ability to differentiate into cardiomyocytes, thus can serve as unlimited source of cells for heart tissue replacement. PSC derived cardiomyocytes can be applied in various areas, such as cell transplantation for the treatment of myocardial infarction, cardiovascular drug screening, drug toxicology analysis, and establishment of heart disease models. However, cardiomyocytes derived from PSCs are composed of three cell types and can not be used directly in the transplantation. Among the three cell types, ventricular myocyte is the most valuable one for clinic applications. However, how to control the differentiation of ventricular cells from cardiac progenitor is a major challenge. Based on bioinformatic analysis of developmental biology studies, five transcriptional factors, namely NKX2.5, dHAND, HEY2, IRX4 and Foxa2, have been identified as ventricular myocyte specific. In this proposal, we intend to adopt a novel protein delivery technology to deliver the four transcription factors into cardiac progenitor cells, with the goal to enhance the efficiency of ventricular myocyte differentiation. Ultimately, a differentiation method that is suitable for large-scale preparation of ventricular myocytes will be established. Safety issues related to the use of T3SS mediated protein delivery has been well addressed and the method is not only high in efficiency but also low in cost, thus easily adaptable to the large scale production processes.
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专利列表
Endoribonuclease YbeY Is Essential for RNA Processing and Virulence in Pseudomonas aeruginosa
内切核糖核酸酶 YbeY 对于铜绿假单胞菌的 RNA 加工和毒力至关重要
DOI:10.1128/mbio.00659-20
发表时间:2020-05-01
期刊:MBIO
影响因子:6.4
作者:Xia, Yushan;Weng, Yuding;Wu, Weihui
通讯作者:Wu, Weihui
DOI:10.3389/fcimb.2023.1267748
发表时间:2023
期刊:Frontiers in cellular and infection microbiology
影响因子:5.7
作者:
通讯作者:
DOI:10.1128/spectrum.03239-22
发表时间:2023-02-14
期刊:Microbiology spectrum
影响因子:3.7
作者:
通讯作者:
DOI:10.1128/aem.02171-20
发表时间:2021-03-01
期刊:APPLIED AND ENVIRONMENTAL MICROBIOLOGY
影响因子:4.4
作者:Xia, Yushan;Xu, Congjuan;Wu, Weihui
通讯作者:Wu, Weihui
铜绿假单胞菌 ExoS 毒素蛋白诱导的细胞凋亡信号通路研究
  • 批准号:
    31370167
  • 项目类别:
    面上项目
  • 资助金额:
    80.0万元
  • 批准年份:
    2013
  • 负责人:
    金守光
  • 依托单位:
铜绿假单胞菌Ⅲ型蛋白分泌系统的表达调控机制
  • 批准号:
    31170128
  • 项目类别:
    面上项目
  • 资助金额:
    58.0万元
  • 批准年份:
    2011
  • 负责人:
    金守光
  • 依托单位:
国内基金
海外基金