Altered neuroepithelial morphogenesis and migration defects in iPSC-derived cerebral organoids and 2D neural stem cells in familial bipolar disorder

Kruttika Phalnikar, M. Srividya, S. Mythri, N. S. Vasavi, Archisha Ganguly, Aparajita Kumar, Padmaja S, Kishan Kalia, Srishti S Mishra, S. Dhanya, P. Paul, B. Holla, Suhas Ganesh, Puli Chandramouli Reddy, R. Sud, B. Viswanath, Bhavana Muralidharan
{"title":"Altered neuroepithelial morphogenesis and migration defects in iPSC-derived cerebral organoids and 2D neural stem cells in familial bipolar disorder","authors":"Kruttika Phalnikar, M. Srividya, S. Mythri, N. S. Vasavi, Archisha Ganguly, Aparajita Kumar, Padmaja S, Kishan Kalia, Srishti S Mishra, S. Dhanya, P. Paul, B. Holla, Suhas Ganesh, Puli Chandramouli Reddy, R. Sud, B. Viswanath, Bhavana Muralidharan","doi":"10.1093/oons/kvae007","DOIUrl":null,"url":null,"abstract":"Abstract Bipolar disorder (BD) is a severe mental illness that can result from neurodevelopmental aberrations, particularly in familial BD, which may include causative genetic variants. In the present study, we derived cortical organoids from BD patients and healthy (control) individuals from a clinically dense family in the Indian population. Our data reveal that the patient organoids show neurodevelopmental anomalies, including organisational, proliferation and migration defects. The BD organoids show a reduction in both the number of neuroepithelial buds/cortical rosettes and the ventricular zone size. Additionally, patient organoids show a lower number of SOX2-positive and EdU-positive cycling progenitors, suggesting a progenitor proliferation defect. Further, the patient neurons show abnormal positioning in the ventricular/intermediate zone of the neuroepithelial bud. Transcriptomic analysis of control and patient organoids supports our cellular topology data and reveals dysregulation of genes crucial for progenitor proliferation and neuronal migration. Lastly, time-lapse imaging of neural stem cells in 2D in vitro cultures reveals abnormal cellular migration in BD samples. Overall, our study pinpoints a cellular and molecular deficit in BD patient-derived organoids and neural stem cell cultures.","PeriodicalId":74386,"journal":{"name":"Oxford open neuroscience","volume":"103 6","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oxford open neuroscience","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/oons/kvae007","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Abstract Bipolar disorder (BD) is a severe mental illness that can result from neurodevelopmental aberrations, particularly in familial BD, which may include causative genetic variants. In the present study, we derived cortical organoids from BD patients and healthy (control) individuals from a clinically dense family in the Indian population. Our data reveal that the patient organoids show neurodevelopmental anomalies, including organisational, proliferation and migration defects. The BD organoids show a reduction in both the number of neuroepithelial buds/cortical rosettes and the ventricular zone size. Additionally, patient organoids show a lower number of SOX2-positive and EdU-positive cycling progenitors, suggesting a progenitor proliferation defect. Further, the patient neurons show abnormal positioning in the ventricular/intermediate zone of the neuroepithelial bud. Transcriptomic analysis of control and patient organoids supports our cellular topology data and reveals dysregulation of genes crucial for progenitor proliferation and neuronal migration. Lastly, time-lapse imaging of neural stem cells in 2D in vitro cultures reveals abnormal cellular migration in BD samples. Overall, our study pinpoints a cellular and molecular deficit in BD patient-derived organoids and neural stem cell cultures.
家族性躁郁症中 iPSC 衍生的脑器官组织和二维神经干细胞的神经上皮形态发生改变和迁移缺陷
摘要 双相情感障碍(BD)是一种严重的精神疾病,可由神经发育异常导致,尤其是在家族性双相情感障碍中,可能包括致病基因变异。在本研究中,我们从躁狂症患者和健康(对照)个体中提取了皮质器官组织,这些患者来自印度人口中的一个临床密集型家族。我们的数据显示,患者的器官组织显示出神经发育异常,包括组织、增殖和迁移缺陷。BD患者的器官组织显示神经上皮芽/皮质花环的数量和脑室区的大小均有所减少。此外,患者器官组织显示 SOX2 阳性和 EdU 阳性的循环祖细胞数量较少,这表明祖细胞增殖存在缺陷。此外,患者的神经元在神经上皮芽的室间/中间区定位异常。对照组和患者器官组织的转录组分析支持了我们的细胞拓扑数据,并揭示了对祖细胞增殖和神经元迁移至关重要的基因失调。最后,二维体外培养神经干细胞的延时成像显示,BD样本中的细胞迁移异常。总之,我们的研究指出了BD患者衍生的器官组织和神经干细胞培养物的细胞和分子缺陷。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信