Department of Biotechnology
inStem (Institute for Stem Cell Science and Regenerative Medicine)

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

Publication Type

Journal Article

Date of Publication

January 1, 2024

Journal

Oxford open neuroscience

Volume/Issue

3

ISSN

2753-149X

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.

Alternate Journal

Oxf Open Neurosci

PubMed ID

38638145

PubMed Central ID

PMC11024480

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