Lee Ju-Hyun, Shaker Mohammed R, Park Si-Hyung, Sun Woong
Department of Anatomy, Brain Korea 21 Plus Program for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
Int J Stem Cells. 2023 Nov 30;16(4):385-393. doi: 10.15283/ijsc23012. Epub 2023 Aug 30.
In vertebrates, the entire central nervous system is derived from the neural tube, which is formed through a conserved early developmental morphogenetic process called neurulation. Although the perturbations in neurulation caused by genetic or environmental factors lead to neural tube defects (NTDs), the most common congenital malformation and the precise molecular pathological cascades mediating NTDs are not well understood. Recently, we have developed human spinal cord organoids (hSCOs) that recapitulate some aspects of human neurulation and observed that valproic acid (VPA) could cause neurulation defects in an organoid model. In this study, we identified and verified the significant changes in cell-cell junctional genes/proteins in VPA-treated organoids using transcriptomic and immunostaining analysis. Furthermore, VPA-treated mouse embryos exhibited impaired gene expression and NTD phenotypes, similar to those observed in the hSCO model. Collectively, our data demonstrate that hSCOs provide a valuable biological resource for dissecting the molecular pathways underlying the currently unknown human neurulation process using destructive biological analysis tools.
在脊椎动物中，整个中枢神经系统起源于神经管，神经管是通过一种称为神经胚形成的保守早期发育形态发生过程形成的。尽管遗传或环境因素引起的神经胚形成扰动会导致神经管缺陷（NTDs），这是最常见的先天性畸形，但介导NTDs的精确分子病理级联反应尚未得到充分了解。最近，我们开发了人类脊髓类器官（hSCOs），它概括了人类神经胚形成的某些方面，并观察到丙戊酸（VPA）可在类器官模型中导致神经胚形成缺陷。在本研究中，我们使用转录组学和免疫染色分析，鉴定并验证了VPA处理的类器官中细胞间连接基因/蛋白质的显著变化。此外，VPA处理的小鼠胚胎表现出基因表达受损和NTD表型，类似于在hSCO模型中观察到的情况。总的来说，我们的数据表明，hSCOs为使用破坏性生物学分析工具剖析目前未知的人类神经胚形成过程背后的分子途径提供了宝贵的生物学资源。
