美国宾夕法尼亚大学Guo-li Ming课题组利用切片人类皮质类器官模拟不同的皮质层形成。相关论文于2020年3月5日发表于《细胞-干细胞》杂志上。

他们报道了切片的新皮质类器官（SNO）系统，该系统绕过了扩散限制，以防止长期培养后细胞死亡。这种方法导致持续的神经发生并形成扩展的皮质板，该皮质板为神经元和星形胶质细胞建立了明显的上层和深层皮质层，类似于孕晚期胚胎人类新皮层。使用SNO系统，他们进一步确定WNT /β-catenin信号在调节人类皮层神经元亚型命运规范中的关键作用，该过程在患者诱导多能干细胞（iPSC）来源的SNOs被精神病相关遗传突变破坏。这些结果表明，SNOs可用于研究以前无法研究的人特异性晚期皮质发育和与疾病相关的机制。

研究人员表示，人脑类器官通过整合胚胎脑的结构，为建模发育和疾病提供了独特的平台。但是，当前的类器官形成受到内部缺氧和由于表面扩散不足导致的细胞死亡的限制，从而阻止了类似于晚期发育阶段的结构的产生。

附：英文原文

Title: Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation

Author: Xuyu Qian, Yijing Su, Christopher D. Adam, Andre U. Deutschmann, Sarshan R. Pather, Ethan M. Goldberg, Kenong Su, Shiying Li, Lu Lu, Fadi Jacob, Phuong T.T. Nguyen, Sooyoung Huh, Ahmet Hoke, Sarah E. Swinford-Jackson, Zhexing Wen, Xiaosong Gu, R. Christopher Pierce, Hao Wu, Lisa A. Briand, H. Isaac Chen, John A. Wolf, Hongjun Song, Guo-li Ming

Issue&Volume: 2020-03-05

Abstract: Human brain organoids provide unique platforms for modeling development and diseasesby recapitulating the architecture of the embryonic brain. However, current organoidmethods are limited by interior hypoxia and cell death due to insufficient surfacediffusion, preventing generation of architecture resembling late developmental stages.Here, we report the sliced neocortical organoid (SNO) system, which bypasses the diffusionlimit to prevent cell death over long-term cultures. This method leads to sustainedneurogenesis and formation of an expanded cortical plate that establishes distinctupper and deep cortical layers for neurons and astrocytes, resembling the third trimesterembryonic human neocortex. Using the SNO system, we further identify a critical roleof WNT/β-catenin signaling in regulating human cortical neuron subtype fate specification,which is disrupted by a psychiatric-disorder-associated genetic mutation in patientinduced pluripotent stem cell (iPSC)-derived SNOs. These results demonstrate the utilityof SNOs for investigating previously inaccessible human-specific, late-stage corticaldevelopment and disease-relevant mechanisms.

DOI: 10.1016/j.stem.2020.02.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30055-2