瑞士弗雷德里希米歇尔生物医学研究所Prisca Liberali团队揭示小鼠类原肠胚的多模态表征。该项研究成果于2023年5月19日在线发表在《细胞—干细胞》杂志上。

利用单细胞基因组分析，研究人员提供了一个资源，映射出类原肠胚发育过程中的细胞状态和类型，并将其与体内胚胎进行比较。研究人员开发了一个高通量的处理和成像方案，在类原肠胚发育过程中对对称性的破坏进行空间监测，并报告了多能性的早期空间变化，其决定了对Wnt激活的二元反应。尽管类原肠胚核心的细胞恢复了多能性，但外围的细胞成为原条样。这两个群体随后打破了径向对称性，开始了轴向延伸。通过进行一个化合物筛选，扰乱数以千计的胚胎，研究人员得出了一个表型景观，并推断出了遗传相互作用的网络。最后，通过使用双重Wnt调控，研究人员改善了现有类原肠胚模型中前部结构的形成。这项工作提供了一个资源，可用于了解类原肠胚如何在体外发育和产生复杂的模式。

据介绍，类原肠胚是由多能干细胞生成的三维结构，再现了胚胎模式形成的基本原则。

附：英文原文

Title: Multimodal characterization of murine gastruloid development

Author: Simon Suppinger, Marietta Zinner, Nadim Aizarani, Ilya Lukonin, Raphael Ortiz, Chiara Azzi, Michael B. Stadler, Stefano Vianello, Giovanni Palla, Hubertus Kohler, Alexandre Mayran, Matthias P. Lutolf, Prisca Liberali

Issue&Volume: 2023-05-19

Abstract: Gastruloids are 3D structures generated from pluripotent stem cells recapitulating fundamental principles of embryonic pattern formation. Using single-cell genomic analysis, we provide a resource mapping cell states and types during gastruloid development and compare them with the in vivo embryo. We developed a high-throughput handling and imaging pipeline to spatially monitor symmetry breaking during gastruloid development and report an early spatial variability in pluripotency determining a binary response to Wnt activation. Although cells in the gastruloid-core revert to pluripotency, peripheral cells become primitive streak-like. These two populations subsequently break radial symmetry and initiate axial elongation. By performing a compound screen, perturbing thousands of gastruloids, we derive a phenotypic landscape and infer networks of genetic interactions. Finally, using a dual Wnt modulation, we improve the formation of anterior structures in the existing gastruloid model. This work provides a resource to understand how gastruloids develop and generate complex patterns in vitro.

DOI: 10.1016/j.stem.2023.04.018

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00170-4