法国莫林研究所Stéphane Nedelec研究团队建立了人躯干器官发生的自组织模型，概述了脊髓和脊柱共形态发生。2023年9月14日出版的《自然—生物技术》杂志发表了这项成果。

他们报告了人类躯干样结构的产生，这些结构模拟了人类脊柱和脊髓的共形态发生、模式和分化。他们确定了人类多能干细胞的分化条件，有利于形成胚胎样的延伸前后轴(AP)。单细胞和空间转录组学表明，体细胞和脊髓分化轨迹沿着这条轴组织，并可以在细胞外基质添加后自组装成由体细胞包围的神经管。形态发生与AP模式机制相结合，导致在器官发生的后期阶段，神经亚型沿着神经管形成体内样阵列，由神经元投射接触的脊柱和肌肉祖细胞包围。

这种躯干发育的综合系统表明，在人体类器官中可以实现类似体内的多组织共形态发生和终末细胞类型的地形组织，为更复杂的器官发生模式的发展打开了窗口。

据介绍，人类器官发生的综合体外模型需要阐明发育和疾病背后的多系统事件。

附：英文原文

Title: Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis

Author: Gribaudo, Simona, Robert, Rmi, van Sambeek, Bjrn, Mirdass, Camil, Lyubimova, Anna, Bouhali, Kamal, Ferent, Julien, Morin, Xavier, van Oudenaarden, Alexander, Nedelec, Stphane

Issue&Volume: 2023-09-14

Abstract: Integrated in vitro models of human organogenesis are needed to elucidate the multi-systemic events underlying development and disease. Here we report the generation of human trunk-like structures that model the co-morphogenesis, patterning and differentiation of the human spine and spinal cord. We identified differentiation conditions for human pluripotent stem cells favoring the formation of an embryo-like extending antero-posterior (AP) axis. Single-cell and spatial transcriptomics show that somitic and spinal cord differentiation trajectories organize along this axis and can self-assemble into a neural tube surrounded by somites upon extracellular matrix addition. Morphogenesis is coupled with AP patterning mechanisms, which results, at later stages of organogenesis, in in vivo-like arrays of neural subtypes along a neural tube surrounded by spine and muscle progenitors contacted by neuronal projections. This integrated system of trunk development indicates that in vivo-like multi-tissue co-morphogenesis and topographic organization of terminal cell types can be achieved in human organoids, opening windows for the development of more complex models of organogenesis. A patterned neural tube and somites in an embryonic context are generated in vitro.

DOI: 10.1038/s41587-023-01956-9

Source: https://www.nature.com/articles/s41587-023-01956-9