二维类胃细胞扩展培养以模拟人类中胚层发育，这一成果由密歇根大学医学院Idse Heemskerk小组经过不懈努力而取得。2025年5月7日出版的《自然—方法学》杂志发表了这一最新研究成果。

在这里，课题组报告了一个延长至10天的二维胃原体模型。该课题组发现了一个高度可复制的形态发生阶段在2到4从原始的条纹状区域直接迁移到外胚层下面的中胚层的天数。多种类型的中胚层具有显著的空间组织，包括菌落边缘的侧板中胚层样细胞和菌落内部的近轴中胚层样细胞。单细胞转录组学显示，这些细胞与人类和非人灵长类动物胚胎的中胚层细胞有很强的相似性。他们的研究结果表明，2D类胃原质扩展培养为人类中胚层分化和形态发生提供了一个强大的模型。

据了解，用BMP4处理的微图型人多能干细胞（二维（2D）原肠样细胞）是最广泛主题的人原肠胚干细胞模型之一。由于其简单性和可重复性，该系统是组织模式高通量定量研究的理想选择，并已导致对哺乳动物原肠胚形成机制的许多见解。然而，二维类胃原质仅被研究了约2在此之前的协议中，由于失去组织而导致的天数。

附：英文原文

Title: Extended culture of 2D gastruloids to model human mesoderm development

Author: Chen, Bohan, Khan, Hina, Yu, Zhiyuan, Yao, LiAng, Freeburne, Emily, Jo, Kyoung, Johnson, Craig, Heemskerk, Idse

Issue&Volume: 2025-05-07

Abstract: Micropatterned human pluripotent stem cells treated with BMP4 (two-dimensional (2D) gastruloids) are among the most widely used stem cell models for human gastrulation. Due to its simplicity and reproducibility, this system is ideal for high-throughput quantitative studies of tissue patterning and has led to many insights into the mechanisms of mammalian gastrulation. However, 2D gastruloids have been studied only up to about 2days owing to a loss of organization beyond this time with earlier protocols. Here we report an extended 2D gastruloid model to up to 10days. We discovered a phase of highly reproducible morphogenesis between 2 and 4days during which directed migration from the primitive streak-like region gives rise to a mesodermal layer beneath an epiblast-like layer. Multiple types of mesoderm arise with striking spatial organization including lateral plate mesoderm-like cells on the colony border and paraxial mesoderm-like cells further inside the colony. Single-cell transcriptomics showed strong similarity of these cells to mesoderm in human and nonhuman primate embryos. Our results illustrate that extended culture of 2D gastruloids provides a powerful model for human mesoderm differentiation and morphogenesis.

DOI: 10.1038/s41592-025-02669-4

Source: https://www.nature.com/articles/s41592-025-02669-4