近日，奥地利科学院分子生物技术研究所Jürgen Arthur Knoblich等研究人员合作发现，极化的FGF8源在皮层组装体的空间定向细胞群体中指定前额颞部特征。该研究于2024年9月18日在线发表于国际一流学术期刊《自然—方法学》。

研究人员通过将表达成纤维母细胞生长因子8（FGF8）的组织器样结构，与延长的类器官融合，工程化人类皮层组装体，以实现沿纵向类器官轴的FGF8信号的受控调节。

这些极化的皮层组装体形成位置依赖的转录程序，部分匹配体内前后方向的基因表达模式，并且在与颞叶畸形和智力障碍相关的FGFR3基因突变下丧失。通过在单个组装体中产生与额叶和颞叶区域身份相关的空间定向细胞群体，该模型部分重现了发育原图中的早期转录分化，并使研究与人类疾病相关的皮层区域变化成为可能。

据介绍，产生主要皮层细胞类型的类器官，在不同的区室中用于研究皮层发育、演化和疾病。然而，当前系统中缺乏赋予皮层位置和地形信息的形态发生因子梯度，阻碍了复杂表型的研究。

附：英文原文

Title: A polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloids

Author: Bosone, Camilla, Castaldi, Davide, Burkard, Thomas Rainer, Guzman, Segundo Jose, Wyatt, Tom, Cheroni, Cristina, Caporale, Nicol, Bajaj, Sunanjay, Bagley, Joshua Adam, Li, Chong, Sorre, Benoit, Villa, Carlo Emanuele, Testa, Giuseppe, Krenn, Veronica, Knoblich, Jrgen Arthur

Issue&Volume: 2024-09-18

Abstract: Organoids generating major cortical cell types in distinct compartments are used to study cortical development, evolution and disorders. However, the lack of morphogen gradients imparting cortical positional information and topography in current systems hinders the investigation of complex phenotypes. Here, we engineer human cortical assembloids by fusing an organizer-like structure expressing fibroblast growth factor 8 (FGF8) with an elongated organoid to enable the controlled modulation of FGF8 signaling along the longitudinal organoid axis. These polarized cortical assembloids mount a position-dependent transcriptional program that in part matches the in vivo rostrocaudal gene expression patterns and that is lost upon mutation in the FGFR3 gene associated with temporal lobe malformations and intellectual disability. By producing spatially oriented cell populations with signatures related to frontal and temporal area identity within individual assembloids, this model recapitulates in part the early transcriptional divergence embedded in the protomap and enables the study of cortical area-relevant alterations underlying human disorders.

DOI: 10.1038/s41592-024-02412-5

Source: https://www.nature.com/articles/s41592-024-02412-5