美国加州大学旧金山分校Wendell A. Lim等研究人员合作发现，合成组织者细胞通过空间和生化指令引导发育。该项研究成果于2024年12月19日在线发表在《细胞》杂志上。
研究人员设计了形态发生因子分泌的组织者细胞，这些细胞通过细胞粘附自组装，在小鼠胚胎干细胞（ES细胞）周围形成特定的结构。通过诱导组织者细胞分泌形态发生因子WNT3A及其拮抗剂DKK1，研究人员生成了不同范围和陡峭度的形态发生因子梯度。
这些梯度与形态发生结果密切相关：WNT活性从最小值到最大值的范围决定了前后（A-P）轴细胞谱系的分布。值得注意的是，尽管浅梯度的WNT活性导致A-P轴谱系的截断，但却能产生较高分辨率的组织形态，例如与内皮网络相关的跳动的、室腔化的心脏样结构。
因此，合成组织者细胞集成了空间、时间和生化信息，为系统性且灵活地引导ES或其他前体细胞在形态发生领域内朝不同方向发育提供了强有力的工具。
据了解，体外发育主要依赖于通过培养基中的形态发生因子处理前体细胞，因此缺乏类似于自然环境的空间信息。
附：英文原文
Title: Synthetic organizer cells guide development via spatial and biochemical instructions
Author: Toshimichi Yamada, Coralie Trentesaux, Jonathan M. Brunger, Yini Xiao, Adam J. Stevens, Iain Martyn, Petr Kasparek, Neha P. Shroff, Angelica Aguilar, Benoit G. Bruneau, Dario Boffelli, Ophir D. Klein, Wendell A. Lim
Issue&Volume: 2024-12-19
Abstract: In vitro development relies primarily on treating progenitor cells with media-borne morphogens and thus lacks native-like spatial information. Here, we engineer morphogen-secreting organizer cells programmed to self-assemble, via cell adhesion, around mouse embryonic stem (ES) cells in defined architectures. By inducing the morphogen WNT3A and its antagonist DKK1 from organizer cells, we generated diverse morphogen gradients, varying in range and steepness. These gradients were strongly correlated with morphogenetic outcomes: the range of minimum-maximum WNT activity determined the resulting range of anterior-to-posterior (A-P) axis cell lineages. Strikingly, shallow WNT activity gradients, despite showing truncated A-P lineages, yielded higher-resolution tissue morphologies, such as a beating, chambered cardiac-like structure associated with an endothelial network. Thus, synthetic organizer cells, which integrate spatial, temporal, and biochemical information, provide a powerful way to systematically and flexibly direct the development of ES or other progenitor cells in different directions within the morphogenetic landscape.
DOI: 10.1016/j.cell.2024.11.017
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01323-0