生物系统科学与工程系Barbara Treutlein研究组在研究中取得进展。他们报道了人类早期脑类器官发育的形态动力学。相关论文于2025年6月18日发表在《自然》杂志上。

在这里，该团队对由荧光标记的人类诱导多能干细胞产生的无引导脑类器官建立了长期的、活的光片显微镜，这使得在类器官发育的几周内跟踪组织形态、细胞行为和亚细胞特征成为可能。该课题组提供了一种新的双通道，多马赛克和多蛋白质标记策略，结合计算解复用方法，可以同时量化类器官发育过程中不同的亚细胞特征。研究小组跟踪肌动蛋白、微管蛋白、质膜、核细胞和核包膜动力学，并量化细胞形态和排列在组织状态转变过程中的变化，包括神经上皮诱导、成熟、流明化和脑区域化。在影像学和单细胞转录组模式的基础上，该团队发现发育中的神经上皮内的管腔扩张和细胞形态组成与涉及细胞外基质通路调节因子和机械传感的基因表达程序的调节有关。小组发现，外部提供的基质可以增强管腔扩张和端脑形成，而在没有外部基质的情况下生长的非引导类器官会改变形态，增加神经嵴和尾状组织的特性。基质诱导的区域引导和管腔形态发生与WNT和Hippo （YAP1）信号通路有关，包括WNT配体分泌介质（WLS）的空间限制性诱导，这标志着最早出现的非端脑脑区。总之，他们的工作为研究人类大脑形态动力学提供了一个突破口，并支持了一种观点，即矩阵连接的机械传感动力学在大脑区域化过程中起着核心作用。

研究人员表示，脑类器官使人类大脑发育的机制研究成为可能，并为探索无约束发育系统中的自组织提供了机会。

附：英文原文

Title: Morphodynamics of human early brain organoid development

Author: Jain, Akanksha, Gut, Gilles, Sanchis-Calleja, Ftima, Tschannen, Reto, He, Zhisong, Luginbhl, Nicolas, Zenk, Fides, Chrisnandy, Antonius, Streib, Simon, Harmel, Christoph, Okamoto, Ryoko, Santel, Malgorzata, Seimiya, Makiko, Holtackers, Ren, Rohland, Juliane K., Jansen, Sophie Martina Johanna, Lutolf, Matthias P., Camp, J. Gray, Treutlein, Barbara

Issue&Volume: 2025-06-18

Abstract: Brain organoids enable the mechanistic study of human brain development and provide opportunities to explore self-organization in unconstrained developmental systems1,2,3. Here we establish long-term, live light-sheet microscopy on unguided brain organoids generated from fluorescently labelled human induced pluripotent stem cells, which enables tracking of tissue morphology, cell behaviours and subcellular features over weeks of organoid development4. We provide a novel dual-channel, multi-mosaic and multi-protein labelling strategy combined with a computational demultiplexing approach to enable simultaneous quantification of distinct subcellular features during organoid development. We track actin, tubulin, plasma membrane, nucleus and nuclear envelope dynamics, and quantify cell morphometric and alignment changes during tissue-state transitions including neuroepithelial induction, maturation, lumenization and brain regionalization. On the basis of imaging and single-cell transcriptome modalities, we find that lumenal expansion and cell morphotype composition within the developing neuroepithelium are associated with modulation of gene expression programs involving extracellular matrix pathway regulators and mechanosensing. We show that an extrinsically provided matrix enhances lumen expansion as well as telencephalon formation, and unguided organoids grown in the absence of an extrinsic matrix have altered morphologies with increased neural crest and caudalized tissue identity. Matrix-induced regional guidance and lumen morphogenesis are linked to the WNT and Hippo (YAP1) signalling pathways, including spatially restricted induction of the WNT ligand secretion mediator (WLS) that marks the earliest emergence of non-telencephalic brain regions. Together, our work provides an inroad into studying human brain morphodynamics and supports a view that matrix-linked mechanosensing dynamics have a central role during brain regionalization.

DOI: 10.1038/s41586-025-09151-3

Source: https://www.nature.com/articles/s41586-025-09151-3