Fig. 1: Modelling synaptic circuits for pre-clinical drug screening using iPSC-derived neuronal cultures of MPS IIIA.
From: Modelling synaptic dysfunction in childhood dementia using human iPSC-derived cortical networks
A Schematic timeline of stages and factors used to generate functional iPSC-derived cortical neuron cultures. Fibroblasts were obtained from patients and age-matched neurotypical controls for iPSC reprogramming before undergoing cortical differentiation and maturation. B Quantificaition of gene expression using qRT-PCR was completed for fibroblasts, human iPSCs, neural progenitor cells and neurons (y-axis) with their respective cell type-specific markers (x-axis) to confirm cell identity. C snRNAseq of day 120 cortical playground neurotypical and MPS IIIA cultures highlighting the major cell types present. Pink indicates excitatory neurons; blue indicates inhibitory neurons; green indicates immature neurons; yellow indicates radial glia; maroon indicates astrocytes; purple indicates oligodendrocyte progenitor cells (OPC). D Experiments utilised a combination of the individual cell lines and the playground model, where neurotypical donor (grey) and MPS IIIA patient (red) post mitotic 14-day neurons were combined. Created in BioRender. Bardy, C. (2026) https://BioRender.com/d85fq44. See also Supplementary Figs. 3–6. Source data are provided as a Source Data file. BDNF brain-derived neurotrophic factor, FGF2 fibroblast growth factor 2, GDNF glial cell line-derived neurotrophic factor, IGF Insulin-like growth factor, hPSC human pluripotent stem cell, MPS IIIA mucopolysaccharidosis type IIIA, NPC neural progenitor cell, PSC pluripotent stem cell, snRNAseq single nuclei RNA sequencing; OPC oligodendrocyte progenitor cell, WT wild type, KO knock out.
