《生命科学》 2026, 38(9): 1535-1548

灵长类早期胚胎发育规律解析与体外模拟

郭致远^1,2,3 , 吴庭逸^1,2,3 , 王红梅^1,2,3,*

¹中国科学院动物研究所，器官再生与智造全国重点实验室，北京 100101 ²中国科学院大学，北京 100049 ³北京干细胞与再生医学研究院，北京 100101

摘　要：

早期胚胎发育是决定全生命周期健康的关键事件。然而，受限于人类体内发育的胚胎难于被观察和研究以及胚胎体外培养的严格伦理界限，当前有关早期胚胎发育的时空动态调控以及构建体外研究模型等方面仍面临巨大挑战。为此，本文系统回顾了灵长类（人和非人灵长类）早期胚胎发育的关键细胞和分子事件，并探讨了基于干细胞的胚胎模型（“类胚胎”）的构建，以及计算生物学在模型优化中的前置预测作用。本文旨在确立以发育规律为导向、以体外模拟为手段的研究范式，为未来搭建标准化、高保真的发育与疾病研究模型提供系统参考。

通讯作者：王红梅 , Email:wanghm@ioz.ac.cn

Elucidation and in vitro modeling of early primate embryonic development

GUO Zhi-Yuan^1,2,3 , WU Ting-Yi^1,2,3 , WANG Hong-Mei^1,2,3,*

¹Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China ²University of Chinese Academy of Sciences, Beijing 100049, China ³Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China

Abstract:

Early embryonic development is a core biological event that dictates lifelong health. However, directly elucidating the dynamic morphogenetic mechanisms of human embryos in vivo remains highly challenging due to  technical barriers and strict ethical constraints. In recent years, breakthroughs in single-cell and spatial multi-omics, coupled with the evolution of in vitro culture (IVC) systems, have driven a paradigm shift in this field—transitioning from static in vivo physiological profiling to dynamic in vitro reconstruction. This review aims to systematically summarize recent advances in early primate embryogenesis, exploring the integration of in vivo developmental principles  with in vitro modeling strategies to provide a rigorous theoretical framework for establishing high-fidelity developmental and drug-screening models. We first delineate the high-resolution, multi-omic landscapes of natural embryos, illustrating their crucial role in establishing molecular benchmarks for key developmental events, including peri-implantation lineage specification, gastrulation, and early organogenesis. Next, we systematically trace the technological evolution of early embryonic IVC systems. We highlight the critical transition from human periimplantation models to the prolonged IVC of non-human primate embryos, which effectively bypasses traditional temporal barriers and enables the functional validation of specific molecular pathways. Building upon these foundations, we discuss the advancement of stem cell-based embryo models (SCBEMs) and emphasize the pivotal, navigational role of computational biology. Despite substantial progress in the in vitro simulation of early embryogenesis, the establishment of highly reductive models capable of smoothly advancing into early organogenesis is still hindered by two primary bottlenecks: insufficient integration of multi-modal omics and the absence of a physiological maternal-fetal microenvironment. To overcome these limitations, future research must advance synergistically in two dimensions. First, it is imperative to deepen cross-modal omics profiling—incorporating epigenetics, spatial metabolomics, and biomechanics—to provide precise priori parameters for high-order models.  Second, leveraging microfluidics and bioengineering technologies to systematically reconstruct the in vitro maternal-fetal interface is essential. This includes simulating the three-dimensional mechanotransduction of the extracellular matrix and assembling early vascular networks to facilitate maternal-fetal metabolic exchange. Guided by developmental principles and executed through engineering reconstruction, this mechanistic approach will profoundly advance our understanding of implantation failure, recurrent pregnancy loss, and congenital birth defects. Ultimately, while strictly adhering to bioethical guidelines, these collective efforts will lay a solid empirical foundation for the standardized application of highthroughput human disease and drug-screening models. 

Communication Author：WANG Hong-Mei , Email:wanghm@ioz.ac.cn