Zhang Xiao-Zuo, Huo Hai-Qin, Zhu Yu-Qing, Feng Hao-Yang, Jiao Jiao, Tan Jian-Xin, Wang Yan, Hu Ping, Xu Zheng-Feng
Department of Prenatal Diagnosis, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.
Front Cell Neurosci. 2022 May 16;16:888152. doi: 10.3389/fncel.2022.888152. eCollection 2022.
The ability of human pluripotent stem cells (hPSCs) to specialize in neuroepithelial tissue makes them ideal candidates for use in the disease models of neural tube defects. In this study, we cultured hPSCs in suspension with modified neural induction method, and immunostaining was applied to detect important markers associated with cell fate and morphogenesis to verify the establishment of the neural tube model . We carried out the drug experiments to further investigate the toxicity of valproic acid (VPA) exposure and the potential protective effect of folic acid (FA). The results demonstrated that neural rosette undergoes cell fate speciation and lumen formation accompanied by a spatiotemporal shift in the expression patterns of cadherin, indicating the model was successfully established. The results showed that VPA caused morphogenesis inhibition of lumen formation by altering cytoskeletal function and cell polarization, which could be rescued by FA supplement.
人类多能干细胞（hPSCs）分化为神经上皮组织的能力使其成为神经管缺陷疾病模型的理想候选者。在本研究中，我们采用改良的神经诱导方法将hPSCs进行悬浮培养，并应用免疫染色检测与细胞命运和形态发生相关的重要标志物，以验证神经管模型的建立。我们进行了药物实验，以进一步研究丙戊酸（VPA）暴露的毒性以及叶酸（FA）的潜在保护作用。结果表明，神经玫瑰花结经历细胞命运特化和管腔形成，同时钙黏蛋白表达模式发生时空变化，表明模型成功建立。结果显示，VPA通过改变细胞骨架功能和细胞极化导致管腔形成的形态发生抑制，补充FA可挽救这种抑制作用。
