研究动态
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自组织模型在人体躯干器官发生过程中回放脊髓和脊柱的共同发生形态的情况。

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

发表日期:2023 Sep 14
作者: Simona Gribaudo, Rémi Robert, Björn van Sambeek, Camil Mirdass, Anna Lyubimova, Kamal Bouhali, Julien Ferent, Xavier Morin, Alexander van Oudenaarden, Stéphane Nedelec
来源: Stem Cell Research & Therapy

摘要:

需要整合体外人体器官发育模型来阐明发育和疾病背后的多系统事件。本文报告了生成类似人胸部结构的人类组织模型,用于模拟人脊柱和脊髓的共同形态发生、分型和分化过程。我们确定了有利于人类多能干细胞形成类似胚胎的前-后 (AP) 轴的分化条件。单细胞和空间转录组学研究表明,索状和脊髓分化轨迹沿着该轴组织,并在加入细胞外基质后可以自组织成为神经管,周围被节胚组成。形态发生与 AP 形态模式机制相结合,在器官发生的后期,形成了类似体内的神经亚型沿着由脊髓和肌肉祖细胞组成、与神经突起接触的神经管呈阵列状分布。这种整合的躯干发育系统表明,在人体器官样物质中可以实现类似体内的多组织共同形态发生和终端细胞类型的拓扑组织,为更复杂的器官发生模型的发展提供了新的突破口。© 2023. 作者,独家授权给 Springer Nature America, Inc.
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.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.