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

TL;DR

This study explores how citalopram, an antidepressant used during pregnancy, affects early brain development in human embryonic stem cells.

Contribution

The study identifies specific genes dysregulated by citalopram during neuronal differentiation, linking them to neurodevelopment and depression.

Findings

Citalopram exposure alters gene expression and DNA methylation of genes like BDNF and GAD2 involved in neurodevelopment and depression.

Single-cell RNA-sequencing revealed distinct stem cell clusters and subtle changes in progenitor subtypes due to citalopram.

Pseudotemporal analysis showed enhanced neuronal differentiation following citalopram exposure.

Abstract

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 BDNF, GDF11, CCL2, STC1, DDIT4 and GAD2. 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.

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