AUTHOR=Spildrejorde Mari , Leithaug Magnus , Samara Athina , Aass Hans Christian D. , Sharma Ankush , Acharya Ganesh , Nordeng Hedvig , Gervin Kristina , Lyle Robert 

TITLE=Citalopram exposure of hESCs during neuronal differentiation identifies dysregulated genes involved in neurodevelopment and depression

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2024.1428538

DOI=10.3389/fcell.2024.1428538

ISSN=2296-634X

ABSTRACT=<p>Selective serotonin reuptake inhibitors (SSRIs), including citalopram, are widely used antidepressants during pregnancy. However, the effects of prenatal exposure to citalopram on neurodevelopment remain poorly understood. We aimed to investigate the impact of citalopram exposure on early neuronal differentiation of human embryonic stem cells using a multi-omics approach. Citalopram induced time- and dose-dependent effects on gene expression and DNA methylation of genes involved in neurodevelopmental processes or linked to depression, such as <italic>BDNF</italic>, <italic>GDF11</italic>, <italic>CCL2</italic>, <italic>STC1</italic>, <italic>DDIT4</italic> and <italic>GAD2</italic>. Single-cell RNA-sequencing analysis revealed distinct clusters of stem cells, neuronal progenitors and neuroblasts, where exposure to citalopram subtly influenced progenitor subtypes. Pseudotemporal analysis showed enhanced neuronal differentiation. Our findings suggest that citalopram exposure during early neuronal differentiation influences gene expression patterns associated with neurodevelopment and depression, providing insights into its potential neurodevelopmental impact and highlighting the importance of further research to understand the long-term consequences of prenatal SSRI exposure.</p>