基础医学与临床2024，Vol.44Issue(6)：786-792,7.DOI:10.16352/j.issn.1001-6325.2024.06.0786
小分子化合物组合改善多能干细胞向脑类器官定向分化的效率
Small molecule compounds improve the targeted differentiation efficiency of cerebral organoids from pluripotent stem cells
摘要
Abstract
Objective To optimize the conditions and improve the efficiency for the differentiation of pluripotent stem cells(PSCs)into cerebral organoids.Methods Based on the induction differentiation system for inducing hu-man embryonic stem cells(hESCs)H9 towards cerebral organoids,a combination of small molecule compounds was added to the developmental stage of neural progenitor cells in the early stage of cerebral organoid differentia-tion,and the efficiency of neural progenitor cell formation,apoptosis and differentiation into neurons in cerebral or-ganoids in the differentiation stage were observed through morphology,the expression of marker genes was detected by RT-qPCR and the effect of small molecule compound combination on cerebral organoids was comprehensively evaluated.Results At the critical stage of neural progenitor cell development(1 d-14 d)of cerebral organoids,dorsomorphine,A83-01,GSK-3β inhibitor CHIR99021 and SMAD inhibitor SB-431542 were successively added to the medium.It could significantly increase the expression of marker genes in the neural progenitor cell stage,promote the formation of specific neural tube-like structures and reduce apoptosis in the central region of cerebral organoids.Conclusions By using the combination of four small molecule compounds,the formation efficiency in early cerebral organoids can be significantly improved,apoptosis in cerebral organoids can be reduced,neuronal formation can be promoted,and tissue structure heterogeneity in the culture process can be reduced.关键词
多能干细胞/小分子化合物/神经分化/脑类器官Key words
pluripotent stem cells/small molecule compounds/neural differentiation/cerebral organoids分类
生物科学引用本文复制引用
朱宛宛,周金娟,修建波..小分子化合物组合改善多能干细胞向脑类器官定向分化的效率[J].基础医学与临床,2024,44(6):786-792,7.基金项目
国家自然科学基金(82101545) （82101545）
中国医学科学院医学与健康科技创新工程(2022-I2M-1-002,2022-I2M-2-001) （2022-I2M-1-002,2022-I2M-2-001）
中央高水平医院临床科研业务费(2022-PUMCH-D-002) （2022-PUMCH-D-002）
