美国华盛顿大学Jay Shendure等研究人员合作发现，维甲酸诱导人类类原肠胚形成后部胚胎样结构。该项研究成果于2024年8月20日在线发表在《自然—细胞生物学》杂志上。

研究人员发现早期使用维甲酸（RA）脉冲处理，并在后期加入Matrigel，可以显著诱导出具有后部胚胎样形态结构的人类类原肠胚，包括神经管、分节的体节以及神经嵴、神经前体、肾前体和肌细胞等多种细胞类型。

通过基于单细胞RNA测序的计算分期分析，研究人员发现人类RA类原肠胚的发育进程超越了其他人类或小鼠胚胎模型，与E9.5的小鼠胚胎和CS11阶段的食蟹猴胚胎对齐。

研究人员利用化学和基因干扰实验进一步确认了WNT和BMP信号在人体环境中调节体节形成和神经管长度的重要性，而转录因子TBX6和PAX3分别在前体节中胚层和神经嵴的形成中起关键作用。展望未来，RA类原肠胚将成为解码早期人类胚胎发育的稳健且可扩展的模型。

据介绍，类原肠胚是一种强大的体外早期人类发育模型。然而，尽管类原肠胚延长并由三种胚层构成，但其形态上并不类似于着床后的早期人类胚胎。

附：英文原文

Title: Retinoic acid induces human gastruloids with posterior embryo-like structures

Author: Hamazaki, Nobuhiko, Yang, Wei, Kubo, Connor A., Qiu, Chengxiang, Martin, Beth K., Garge, Riddhiman K., Regalado, Samuel G., Nichols, Eva K., Pendyala, Sriram, Bradley, Nicholas, Fowler, Douglas M., Lee, Choli, Daza, Riza M., Srivatsan, Sanjay, Shendure, Jay

Issue&Volume: 2024-08-20

Abstract: Gastruloids are a powerful in vitro model of early human development. However, although elongated and composed of all three germ layers, human gastruloids do not morphologically resemble post-implantation human embryos. Here we show that an early pulse of retinoic acid (RA), together with later Matrigel, robustly induces human gastruloids with posterior embryo-like morphological structures, including a neural tube flanked by segmented somites and diverse cell types, including neural crest, neural progenitors, renal progenitors and myocytes. Through in silico staging based on single-cell RNA sequencing, we find that human RA-gastruloids progress further than other human or mouse embryo models, aligning to E9.5 mouse and CS11 cynomolgus monkey embryos. We leverage chemical and genetic perturbations of RA-gastruloids to confirm that WNT and BMP signalling regulate somite formation and neural tube length in the human context, while transcription factors TBX6 and PAX3 underpin presomitic mesoderm and neural crest, respectively. Looking forward, RA-gastruloids are a robust, scalable model for decoding early human embryogenesis.

DOI: 10.1038/s41556-024-01487-8

Source: https://www.nature.com/articles/s41556-024-01487-8