Citalopram Exposure of HESCs During Neuronal Differentiation Identifies Dysregulated Genes Involved in Neurodevelopment and Depression

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2024 Jul 26

PMID 39055655

Authors

Mari Spildrejorde

Magnus Leithaug

Athina Samara

Hans Christian D Aass

Ankush Sharma

Ganesh Acharya

Hedvig Nordeng

Kristina Gervin

Robert Lyle

Affiliations

Soon will be listed here.

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 , , , , and . 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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