Applications of synthetic biology to stem-cell-derived modeling of early embryonic development

YANG Ying; LI Xia; LIU Lizhong

doi:10.12211/2096-8280.2025-013

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Applications of synthetic biology to stem-cell-derived modeling of early embryonic development

Invited Review | 更新时间：2025-07-07

- Applications of synthetic biology to stem-cell-derived modeling of early embryonic development
- Synthetic Biology Journal Vol. 6, Issue 3, Pages: 669-684(2025)
- 作者机构：
  
  1.西湖实验室（生命科学和生物医学浙江省实验室），浙江杭州 310024
  2.西湖大学生命科学学院，浙江杭州 310030
  3.浙江西湖高等研究院生物学研究所，浙江杭州 310024
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2025-013
  CLC： Q81
- Received：03 March 2025，
  
  Revised：2025-05-12，
  
  Published：30 June 2025
- 稿件说明：
移动端阅览
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， 2025， 6（3）： 669-684

YANG Ying， LI Xia， LIU Lizhong. Applications of synthetic biology to stem-cell-derived modeling of early embryonic development［J］. Synthetic Biology Journal， 2025， 6（3）： 669-684
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， 2025， 6（3）： 669-684 DOI： 10.12211/2096-8280.2025-013.

YANG Ying， LI Xia， LIU Lizhong. Applications of synthetic biology to stem-cell-derived modeling of early embryonic development［J］. Synthetic Biology Journal， 2025， 6（3）： 669-684 DOI： 10.12211/2096-8280.2025-013.

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。并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，最后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。

Abstract

Understanding how a fertilized egg develops from a single cell into complex tissues and organs remains a central question in developmental biology. However

in mammals

especially in humans

technical and ethical constraints limit

in utero

investigation of the post-implantation development and

ex utero

culture beyond organogenesis as well. As a result

the molecular and cellular mechanisms underpinning spatiotemporal regulation during these stages remain poorly understand. This knowledge gap underscores the urgent need for high-fidelity

in vitro

models that not only recapitulate

in vivo

developmental processes but also allow for precise experimental perturbations. Recent advances in stem cell-based embryo models and organoids leverage the developmental potential and intrinsic self-organizing capabilities of pluripotent stem cells to mimic aspects of

early embryonic and organ development

offering new platforms for studying those complex processes. Concurrently

synthetic biology provides powerful tools

such as programmable gene circuits

optogenetics

and engineered signaling pathways

to control gene expression

cell differentiation

intercellular communications

and tissue patterning with unprecedented precision. This review highlights recent progress in integrating synthetic biology with

in vitro

models to dissect and reconstitute fundamental mechanisms of embryonic development. By harnessing synthetic biology tools

researchers can now modulate specific pathways with temporal and spatial precision

enabling a deeper understanding of processes such as signal transduction dynamics

cellular adhesion networks

symmetry breaking

and the establishment of polarity. This bottom-up “build-to-learn” approach shifts the paradigm from observational to predictive developmental biology. Such innovations have collectively given rise to the emerging field of synthetic developmental biology. This field not only provides mechanistic insights into developmental events that were previously inaccessible but also opens new avenues for building artificial tissues and structures with tailored functions. We also discuss current limitations in mimicking the morphology and function of natural embryonic structures

emphasizing the need for robust evaluation systems and refined strategies to precisely control cell behavior. Finally

we explore how synthetic developmental biology can elucidate key principles of embryogenesis and accelerate future applications in regenerative medicine.

关键词

Keywords

references

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LIU Lizhong

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Institute of Basic Medical Sciences， Westlake Institute for Advanced Study

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