研究小组开发了类似人类FP （hFpOs）的类器官，并将它们与人类脊髓类器官（hSpOs）组装在一起，生成中线组装体(hMAs）。研究组证明hFpOs促进腹侧模式，交联轴突引导和双边连通性。为了研究中线调节因子，课题组人员分析了hFpOs分泌组，与motheme相比鉴定了27个人类富集的基因。在hMAs的排列CRISPR筛选中，课题组发现GALNT2和PLD3的缺失会损害FP介导的轴突引导。这个平台有望揭示人类特异性神经生物学和疾病的各个方面。
据了解，组织者在发育中的神经系统中协调细胞模式和轴突引导。虽然非人类模型已经导致了关于底板（FP）介导的中线组织的基本发现，但人类FP的实验模型将使该研究组能够深入了解人类神经发育和中线连接。
附：英文原文
Title: Midline assembloids reveal regulators of human axon guidance
Author: Massimo M. Onesto, Neal D. Amin, Chenjie Pan, Xiaoyu Chen, Ji-il Kim, Noah Reis, Sabina Kanton, Alfredo M. Valencia, Zuzana Hudacova, James P. McQueen, Marc Tessier-Lavigne, Sergiu P. Paca
Issue&Volume: 2025-07-17
Abstract: Organizers orchestrate cell patterning and axon guidance in the developing nervous system. Although nonhuman models have led to fundamental discoveries about floor plate (FP)–mediated midline organization, an experimental model of the human FP would enable insights into human neurodevelopment and midline connectivity. Here, we developed organoids resembling human FP (hFpOs) and assembled them with human spinal cord organoids (hSpOs) to generate midline assembloids (hMAs). We demonstrate that hFpOs promote ventral patterning, commissural axon guidance, and bilateral connectivity. To investigate midline regulators, we profiled the hFpO secretome, identifying 27 human-enriched genes compared with mouse. In an arrayed CRISPR screen of hMAs, we discovered that loss of GALNT2 and PLD3 impaired FP–mediated guidance of axons. This platform holds promise for revealing aspects of human-specific neurobiology and disease.
DOI: adq7934
Source: https://www.science.org/doi/10.1126/science.adq7934