Chronic cortisol differentially impacts stem cell-derived astrocytes from major depressive disorder patients.
Kelly J HeardMaxim N ShokhirevCaroline BecronisCallie FredlenderNadia ZahidAmy T LeYuan JiMichelle K SkimeTimothy NelsonDaniel Hall-FlavinRichard M WeinshilboumFred H GageKrishna C VadodariaPublished in: Translational psychiatry (2021)
Major depressive disorder (MDD) is a prevalent psychiatric disorder, and exposure to stress is a robust risk factor for MDD. Clinical data and rodent models have indicated the negative impact of chronic exposure to stress-induced hormones like cortisol on brain volume, memory, and cell metabolism. However, the cellular and transcriptomic changes that occur in the brain after prolonged exposure to cortisol are less understood. Furthermore, the astrocyte-specific contribution to cortisol-induced neuropathology remains understudied. Here, we have developed an in vitro model of "chronic stress" using human induced pluripotent stem cell (iPSC)-derived astrocytes treated with cortisol for 7 days. Whole transcriptome sequencing reveals differentially expressed genes (DEGs) uniquely regulated in chronic cortisol compared to acute cortisol treatment. Utilizing this paradigm, we examined the stress response transcriptome of astrocytes generated from MDD patient iPSCs. The MDD-specific DEGs are related to GPCR ligand binding, synaptic signaling, and ion homeostasis. Together, these data highlight the unique role astrocytes play in the central nervous system and present interesting genes for future study into the relationship between chronic stress and MDD.
Keyphrases
- major depressive disorder
- bipolar disorder
- stress induced
- stem cells
- single cell
- drug induced
- genome wide
- gene expression
- endothelial cells
- electronic health record
- end stage renal disease
- liver failure
- mental health
- transcription factor
- high glucose
- diabetic rats
- induced pluripotent stem cells
- chronic kidney disease
- case report
- ejection fraction
- prognostic factors
- mesenchymal stem cells
- machine learning
- deep learning
- dna methylation
- mechanical ventilation
- blood brain barrier
- patient reported outcomes
- high throughput sequencing
- genome wide identification