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Updated: Jun 19, 2025
Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Citalopram exposure of hESCs during neuronal differentiation identifies dysregulated genes involved in
Mari Spildrejorde1,2,3,4, Magnus Leithaug1,2, Athina Samara5,6,7
1PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
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.
Insights
Prenatal exposure to citalopram, a selective serotonin reuptake inhibitor (SSRI), impacts early neuronal differentiation. This study reveals altered gene expression and DNA methylation, suggesting potential neurodevelopmental effects.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Selective serotonin reuptake inhibitors (SSRIs) are common antidepressants used during pregnancy.
- The neurodevelopmental effects of prenatal SSRI exposure, specifically citalopram, are not fully understood.
Purpose of the Study:
- To investigate the impact of citalopram on the early neuronal differentiation of human embryonic stem cells.
- To explore gene expression and DNA methylation changes associated with citalopram exposure.
Main Methods:
- Utilized a multi-omics approach on human embryonic stem cells.
- Performed single-cell RNA-sequencing and pseudotemporal analysis.
- Examined time- and dose-dependent effects of citalopram.
Main Results:
- Citalopram exposure altered gene expression and DNA methylation of neurodevelopmental and depression-related genes (e.g., BDNF, GAD2).
- Single-cell RNA-sequencing identified subtle influences of citalopram on neuronal progenitor subtypes.
- Pseudotemporal analysis indicated enhanced neuronal differentiation following citalopram exposure.
Conclusions:
- Prenatal citalopram exposure influences gene expression patterns critical for neurodevelopment and linked to depression.
- Findings provide insights into the potential neurodevelopmental impact of citalopram.
- Further research is crucial to understand the long-term consequences of prenatal SSRI exposure.
