Altered Neuroepithelial Morphogenesis and Migration Defects in IPSC-derived Cerebral Organoids and 2D Neural Stem Cells in Familial Bipolar Disorder

Overview

Journal Oxf Open Neurosci

Publisher Oxford University Press

Specialty Neurology

Date 2024 Apr 19

PMID 38638145

Authors

Kruttika Phalnikar

M Srividya

S V Mythri

N S Vasavi

Archisha Ganguly

Aparajita Kumar

Padmaja S

Kishan Kalia

Srishti S Mishra

Sreeja Kumari Dhanya

Pradip Paul

Bharath Holla

Suhas Ganesh

Puli Chandramouli Reddy

Reeteka Sud

Biju Viswanath

Bhavana Muralidharan

Affiliations

Soon will be listed here.

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 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.

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