Transcriptome analysis reveals disparate expression of inflammation-related miRNAs and their gene targets in iPSC-astrocytes from people with schizophrenia

Probing the molecular and cellular pathological mechanisms of schizophrenia using human induced pluripotent stem cell models

“…This result also coincides with the decreased expression of T-cell marker, forkhead box p3 transcription factor (FOXP3) in astrocytes. Additionally, a follow-up study investigating gene expression differences via RNA-sequencing identified a decrease in expression of immune related genes, such as, interleukin 23 receptor (IL23R) and interleukin 1 receptor associated kinase 1 (IRKA1) in SCZ iPSC-astrocytes ( Akkouh et al, 2021 ). Altogether, these findings suggest that astrocyte’s ability to regulate inflammation is hampered in SCZ patients, thus further propagating the pathogenic effect of the disease.…”

Current progress in understanding Schizophrenia using genomics and pluripotent stem cells: A Meta-analytical overview

“…However, these events may be interconnected and influence one another. The contribution of glial cells to SCZ pathology was not studied extensively but in a relatively small number of studies (Akkouh et al 2020; Akkouh et al 2021; Windrem et al 2017; Szabo et al 2021). Mice implanted with human iPSC-derived glial cells from SCZ patients were observed to have abnormal behavior including anxiety and reduced social interaction (Windrem et al 2017).…”

The Perspectives of Early Diagnosis of Schizophrenia Through the Detection of Epigenomics-Based Biomarkers in iPSC-Derived Neurons

“…For example, an early study by Brennand et al (2011) showed that differentiated iPSC neurons from a schizophrenic patient had impaired neuronal connectivity, decreased neurite number, expression of synaptic proteins such as PSD-95, and, importantly, altered transcript expression. Similarly, multiple studies have shown reduced levels of neuronal differentiation-associated genes in neural progenitor cells from schizophrenic patient-derived iPSCs ( Yu et al, 2014 ), suggesting a link between altered microRNA profiling ( Zhao et al, 2015 ; Topol et al, 2016 ; Akkouh et al, 2021 ), chromatin openness in which disease variants affecting neurodevelopment reside ( Forrest et al, 2017 ; Zhang et al, 2020 ), and protein expression patterns ( Tiihonen et al, 2019 ). These results demonstrate (1) iPSC-derived neurons, but not other cell-types, from schizophrenia patients faithfully recapitulate many pathological disease features and (2) iPSC-derived neurons may be used to detect uniquely altered transcriptional, epigenetic, and proteome signals that could be utilized as potential biomarkers.…”