The cellular organelles in differentiated glial cells derived from WDR45-mutated induced pluripotent stem cells

초록

In general, microglia and astrocytes assist neurons in maintaining their metabolism, plasticity, and homeostasis. Additionally, oligodendrocytes play a role in facilitating the transfer of electrical signals and contributing to overall metabolic processes. A loss of function or defects in glia have been identified in many neurodegenerative diseases. Consequently, the function of glia is being investigated in the context of neurodegenerative diseases. Beta-propeller protein-associated neurodegeneration (BPAN) is a rare disease that is characterized by the accumulation of iron in the ganglia as a result of a mutation in the WDR45 gene. The disease is accompanied by a number of additional symptoms, including epilepsy, developmental delays, movement dysfunction, behavioral issues, and abnormal brain imaging in early childhood. Moreover, the clinical manifestations of BPAN are linked to demyelination. To investigate the differences between oligodendrocytes in BPAN, induced pluripotent stem cells (iPSCs) were differentiated into oligodendrocyte precursor cells (OPCs) using the protocols developed by Douvaras and Fossati. The differentiation process was confirmed by the expression of neuron and oligodendrocyte markers on days 8, 12, and 56 from the initial induction. The application of confocal microscopy and transmission electron microscopy revealed differences in the lysosomal and lipid content of OPCs after 56 days from the initial induction. The present study demonstrates disparities in the morphology of cellular organelles between OPCs and neurons derived from WDR45 mutant iPSCs and healthy iPSCs. It is therefore hoped that these structural changes during differentiation will provide a basis for establishing a relationship between the cause of BPAN and demyelination.