• 特约评述 •
杨莹1, 李霞1, 刘立中1,2,3
收稿日期:
2025-03-03
修回日期:
2025-05-12
出版日期:
2025-05-14
通讯作者:
刘立中
作者简介:
基金资助:
YANG Ying1, LI Xia1, LIU Lizhong1,2,3
Received:
2025-03-03
Revised:
2025-05-12
Online:
2025-05-14
Contact:
LIU Lizhong
摘要:
早期胚胎发育过程中如何从单细胞合子逐步形成复杂组织与器官,是发育生物学长期关注的核心问题。然而,哺乳动物尤其是人类胚胎着床后的发育因技术和伦理限制而难以直接观测,导致对关键时空调控机制的认识仍然不足。近年来,多能性干细胞衍生的类胚胎和类器官模型迅速发展,为体外模拟早期胚胎发育和器官发生提供了新途径。与此同时,合成生物学借助工程化思维与可编程基因线路,为精确调控细胞分化、信号传递及细胞命运模式化提供了前所未有的技术支持。本文探讨基于干细胞的类胚胎和类器官模型如何融合合成生物学与定量生物学方法,从自下而上的“建物致知”角度探讨关键发育事件的机制。我们还针对目前模型与真实胚胎及器官在形态与功能层面的差距,探讨建立标准化评价体系及发展精准细胞行为调控策略的必要性,并展望了合成发育生物学在干细胞类胚胎与类器官模型中潜在的应用前景。
中图分类号:
杨莹, 李霞, 刘立中. 合成生物学在干细胞早期胚胎发育模型中的应用[J]. 合成生物学, DOI: 10.12211/2096-8280.2025-013.
YANG Ying, LI Xia, LIU Lizhong. Application of synthetic biology approaches to stem-cell-derived models of early embryonic development[J]. Synthetic Biology Journal, DOI: 10.12211/2096-8280.2025-013.
图1 早期胚胎发育及类胚胎与类器官模型(a)人类早期胚胎发育时间轴。人类胚胎发育始于囊胚着床于子宫壁,随后形成由上胚层和下胚层构成的双胚层胚盘。原肠胚形成过程将其转变为三胚层结构:外胚层、中胚层和内胚层,为早期器官发生奠定基础。(b)干细胞类胚胎模型和类器官。作者在此列举了几种具有代表性的干细胞类胚胎模型,能够较好地模拟从着床前、着床期到原肠胚形成及早期器官发生等关键发育阶段,同时也展示了部分具有代表性的类器官模型。由于篇幅所限,未能收录全部相关研究,敬请谅解。
Fig.1 Early embryonic development, embryo models and organoids(a) A timeline of early human embryonic development. Human embryonic development begins with the blastocyst implanting into the uterine wall, followed by the formation of the bilaminar disc composed of the epiblast and hypoblast. Gastrulation then transforms the disc into a trilaminar structure: ectoderm, mesoderm, and endoderm, laying the foundation for early organogenesis. (b) Representative stem cell-based embryo models and organoids. Here are representative stem cell-based embryo models selected by the authors, which recapitulate key developmental stages ranging from pre-implantation and peri-implantation to gastrulation and early organogenesis. Due to space constraints, we regret that not all relevant studies could be included.
图3 光遗传工具在发育生物学中的应用(a)光遗传控制BMP信号通路活性。通过光-氧-电压感应结构域介导的二聚化调控细胞内酪氨酸激酶活性,进而引发SMAD1/5的磷酸化,并促使其进入细胞核以启动BMP下游基因的表达。(b)光遗传控制细胞收缩。光遗传激活的Shroom3通过在顶端连接处招募ROCK,驱动细胞顶端收缩。
Fig. 3 Applications of Optogenetic Tools in Developmental Biology(a) Optogenetic control of BMP signaling pathway activity. Dimerization mediated by the light-oxygen-voltage (LOV) sensing domain regulates intracellular tyrosine kinase activity, leading to SMAD1/5 phosphorylation and their translocation into the nucleus to initiate downstream BMP target gene expression. (b) Optogenetic control of cell contraction. Optogenetically activated Shroom3 drives apical constriction through ROCK recruitment at apical junctions.
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