Establishment of a Model System for Studying Neurodevelopmental Disorders Using Induced Pluripotent Stem Cells Derived From Patients With 22q11.2 Deletion Syndrome
Year: 2024
Type: article
Abstract: 22q11.2 Deletion Syndrome is the most common microdeletion syndrome in humans. It is associated with elevated risk for neurodevelopmental psychiatric disorders and thus represents a powerful genetics-first approach to delineate molecular mechanisms underlying these disorders. Although many animal models mimic human diseases, only limited success has been achieved in revealing molecular mechanisms underlying human brain diseases. Our goal was to establish patient-specific induced pluripotent stem cells (iPSCs) since they represent a powerful tool for establishing in vitro models of disorders. Peripheral blood mononuclear cells of control subjects and patients with 22q11.2 microdeletion were reprogrammed using CytoTune™-iPS 2.0 Sendai Reprogramming Kit. Generated iPSC cell lines were characterized by analyzing their morphology, pluripotency, genomic integrity and the ability to differentiate into three germ layers. iPSCs were differentiated into neural progenitor cells and neurons using Dual-SMAD inhibition method and 3D cerebral organoids in order to analyze neural differentiation in patient-specific background. RNA sequencing was performed to determine differentially expressed gene sets and dysregulated pathways in neural cells derived from patients with 22q11.2 microdeletion. We successfully generated iPSC lines from patients with 22q11.2 microdeletion and healthy individuals, characterized them and differentiated into neural progenitors, neurons and cerebral organoids. List of differentially expressed genes was determined. Generated patient-specific iPSCs represent a powerful model system for studying molecular mechanisms underlying NDDs.
Authors: Drakulić, Danijela, Harwood, Adrian, Petrakis, Spyros, Linden, David, Stevanović, Milena
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7065724340