利用体外自组装拟胚体系统研究细胞间识别和相互作用调控机制

批准号:
31970825
项目类别:
面上项目
资助金额:
60.0 万元
负责人:
韩建永
依托单位:
学科分类:
组织器官稳态维持与再生修复
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
韩建永
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中文摘要
胚胎干细胞、滋养层干细胞和原始内胚层干细胞,在悬浮震荡培养条件下,可以自我形成胚胎样结构即ETX-拟胚体,模拟正常胚胎发育事件,如成腔、原始生殖细胞特化等。这说明胚胎发育过程中,不同细胞的自我识别和相互作用对个体正常发育极为重要。许多原肠胚体内实验无法开展,因而ETX-拟胚体为原肠胚发育研究提供良好体外模型。本项目拟利用ETX-拟胚体,结合干细胞生物学、基因编辑、分子生物学等技术手段,对ETX-拟胚体形成过程中,三种干细胞自我识别、相互作用的分子机制进行研究。以期发现关键调控因子,为胚胎发育研究及临床应用提供理论依据。同时,优化三种干细胞的培养体系,获得初始态干细胞,进一步优化ETX-拟胚体构建体系,使其具有更复杂组织结构,提高其发育潜能,为未来动物育种提供新的思路。本项目研究可以为胚胎不对称分化、中胚层及PGC特化等一系列发育事件提供新模型,为解析组织工程和再生医学提供理论依据。
英文摘要
The embryonic stem cells, trophoblast stem cells and extra-embryonic endoderm stem cells derived from blastocyst, could self-assemble into embryo-like structures (ETX-embryoids) under nonadherent-suspension-shaking system when cultured together at appropriate ratio. The ETX-embryoids can mimic the embryogenesis of natural embryos, such as luminogenesis, PGC specification, which suggests the self-recognition and interaction between different cell types are crucial for natural embryogenesis. However, many experiments cannot be conducted due to the limit cell number in embryos during gastrulation. ETX-embryoids can be regarded as a suitable model for gastrulation research. Our program is going to study the molecular mechanisms of cell self-recognition and interaction with ETX-embryoids, by combining the techniques of stem cell biology, gene editing and molecular biology. We aim to find key regulatory factors and provide theoretical basis for embryogenesis research and clinical application. Meanwhile, we plan to optimize the ETX-embryoid culture system, isolate naïve embryonic stem cells and PE-like stem cells to improve the developmental potential of ETX-embryoids which are capable of giving birth to fetus, proving new ideas for animal breeding in the future. Our study could provide an innovative model for embryonic developmental researches including asymmetry differentiation, mesoderm and PGC specification, and provide theoretical basis and reference for organ regeneration, tissue engineering and regenerative medicine.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1021/acs.orglett.3c01038
发表时间:2023
期刊:Orgnic Letter
影响因子:--
作者:Li Li;Yuezhou Wang;Naixin Chen;Xiaoyang Li;Hanpeng Li;Ling Jin;Yixin Ou;Xiang-Jian Kong;Shugeng Cao;Qingyan Xu;Xiaobing Wu;Jianyong Han;Xianming Deng
通讯作者:Xianming Deng
METTL3-mediated mRNA N(6)-methyladenosine is required for oocyte and follicle development in mice.
METTL3 介导的 mRNA N-6-甲基腺苷是小鼠卵母细胞和卵泡发育所必需的
DOI:10.1038/s41419-021-04272-9
发表时间:2021-10-23
期刊:Cell death & disease
影响因子:9
作者:Mu H;Zhang T;Yang Y;Zhang D;Gao J;Li J;Yue L;Gao D;Shi B;Han Y;Zhong L;Chen X;Wang ZB;Lin Z;Tong MH;Sun QY;Yang YG;Han J
通讯作者:Han J
DOI:10.1093/biolre/ioac119
发表时间:2022-06
期刊:Biology of Reproduction
影响因子:3.6
作者:Jinying Zhang;Minglei Zhi;Dengfeng Gao;Qianqian Zhu;Jie Gao;Gaoxiang Zhu;Suying Cao;Jianyong Han-J
通讯作者:Jinying Zhang;Minglei Zhi;Dengfeng Gao;Qianqian Zhu;Jie Gao;Gaoxiang Zhu;Suying Cao;Jianyong Han-J
Generation and characterization of stable pig pregastrulation epiblast stem cell lines.
稳定猪原肠胚形成前外胚层干细胞系的产生和表征。
DOI:10.1038/s41422-021-00592-9
发表时间:2022-04
期刊:Cell research
影响因子:44.1
作者:Zhi M;Zhang J;Tang Q;Yu D;Gao S;Gao D;Liu P;Guo J;Hai T;Gao J;Cao S;Zhao Z;Li C;Weng X;He M;Chen T;Wang Y;Long K;Jiao D;Li G;Zhang J;Liu Y;Lin Y;Pang D;Zhu Q;Chen N;Huang J;Chen X;Yao Y;Yang J;Xie Z;Huang X;Liu M;Zhang R;Li Q;Miao Y;Tian J;Huang X;Ouyang H;Liu B;Xie W;Zhou Q;Wei H;Liu Z;Zheng C;Li M;Han J
通讯作者:Han J
DOI:10.1111/cpr.13487
发表时间:2023-11
期刊:Cell proliferation
影响因子:8.5
作者:
通讯作者:
WNT信号调控猪原肠化前上胚层干细胞多能性维持的机制
- 批准号:32370846
- 项目类别:面上项目
- 资助金额:50万元
- 批准年份:2023
- 负责人:韩建永
- 依托单位:
猪胚胎干细胞向雄性生殖细胞诱导分化及其调控机制研究
- 批准号:31772601
- 项目类别:面上项目
- 资助金额:60.0万元
- 批准年份:2017
- 负责人:韩建永
- 依托单位:
Tbx3调控小鼠胚胎期乳腺原基发生发育分子机制的研究
- 批准号:31571497
- 项目类别:面上项目
- 资助金额:65.0万元
- 批准年份:2015
- 负责人:韩建永
- 依托单位:
国内基金
海外基金
