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Significance To compare global gene expression features of differentiating human pluripotent stem cell-derived Purkinje cells (hPSC-PCs) and developing mouse Purkinje cells (PCs), we derived hPSC-PCs and compared gene expression datasets from human and mouse PCs. We optimized a differentiation protocol that generated hPSC-PCs most similar in gene expression to mouse P21 PCs. Metagene projection analysis of mouse PC gene expression over postnatal development identified both classical PC marker genes as well as novel mitochondrial and autophagy gene pathways. These key gene expression patterns were conserved in differentiating hPSC-PCs. We further identified differences in timing and expression of key gene sets between mouse and hPSC-PCs and confirmed expression of a novel human PC marker, CD40LG, in human cerebellar tissue.

Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics