玻连蛋白在人诱导多能干细胞早期造血分化中的作用及机制研究
批准号:
82000118
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
沈俊
学科分类:
造血、造血调控与造血微环境
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
沈俊
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中文摘要
玻连蛋白(Vitronectin)是细胞外基质的重要组成成分,已被广泛应用于人诱导多能干细胞(hiPSC)的维持和扩增,但其在造血发育中的作用却鲜有报道。我们前期研究发现,与小鼠基质胶Matrigel相比,Vitronectin能显著促进hiPSC早期造血分化。通过化学成分明确的Vitronectin高效地诱导hiPSC定向造血分化,为血细胞治疗带来了新的策略。本项目拟研究:1)细胞水平上,明确Vitronectin对hiPSC来源的中胚层祖细胞,生血内皮细胞及造血祖细胞分化的影响;2)分子水平上,以整合素αvβ3为切入点,深入探索Vitronectin调节hiPSC定向造血分化的分子机制;3)功能水平上,研究Vitronectin及其介导的αvβ3对造血祖细胞体内外功能的影响。本课题将为人正常造血发育研究及血细胞治疗研究奠定方法学和理论学基础,具有潜在的临床应用前景。
英文摘要
Vitronectin, an important component of the extracellular matrix,has been widely used for the maintenance and expansion of human induced pluripotent stem cells (hiPSCs). However, the effect of vitronectin on hematopoietic development remains unclear. Our previous studies showed that vitronectin significantly promoted early hematopoiesis of hiPSCs. Generation of blood cells from hiPSCs by chemically-defined vitronectin induction would offer a new strategy for blood cell therapy. So we intend to carry out our study as below : 1) At the cellular level, determining the effect of vitronectin on the development of mesodermal progenitor cells, endothelial cells and hematopoietic progenitor cells; 2) At the molecular level, exploring the molecular mechanism of vitronectin and integrin αvβ3 in regulating hematopoietic differentiation of hiPSCs; 3) At the functional level, clarifying the effect of vitronectin and αvβ3 on the function of hematopoietic progenitor cells both in vitro and in vivo. Our study would lay a methodological and theoretical foundation for the exploration of normal hematopoietic development and blood cell therapy.
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DOI:10.1002/jcp.30924
发表时间:2022-11
期刊:Journal of Cellular Physiology
影响因子:5.6
作者:Shuo Zhang;Kengyuan Qu;Shuzhen Lyu;Dixie L. Hoyle;Cory J. Smith;Linzhao Cheng;Tao Cheng;Jun Shen;Zack Z Wang
通讯作者:Shuo Zhang;Kengyuan Qu;Shuzhen Lyu;Dixie L. Hoyle;Cory J. Smith;Linzhao Cheng;Tao Cheng;Jun Shen;Zack Z Wang
Single-cell transcriptome of early hematopoiesis guides arterial endothelial-enhanced functional T cell generation from human PSCs.
早期造血的单细胞转录组指导人类 PSC 生成动脉内皮增强功能性 T 细胞
DOI:10.1126/sciadv.abi9787
发表时间:2021-09-03
期刊:Science advances
影响因子:13.6
作者:Shen J;Xu Y;Zhang S;Lyu S;Huo Y;Zhu Y;Tang K;Mou J;Li X;Hoyle DL;Wang M;Wang J;Li X;Wang ZZ;Cheng T
通讯作者:Cheng T
DOI:10.1111/cpr.13012
发表时间:2021-04
期刊:Cell proliferation
影响因子:8.5
作者:Shen J;Zhu Y;Zhang S;Lyu S;Lyu C;Feng Z;Hoyle DL;Wang ZZ;Cheng T
通讯作者:Cheng T
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