Integrative Genomic Analysis Identifies THAP9 as a Human-Specific Regulator of Oligodendrocyte Differentiation

Oligodendrocyte maturation and myelination are critical processes in human neurodevelopment, and their dysregulation is linked to numerous neurological disorders. While model organisms have provided insight into these processes, human-specific regulatory mechanisms remain poorly understood. This study investigated human THAP9, a protein homologous to the Drosophila P-element transposase, whose function in oligodendrocytes remains unknown. An analysis of RNA-sequencing data and H3K27ac ChIP-sequencing data from oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes (MOs) revealed significant upregulation of THAP9 during oligodendrocyte maturation. Co-expression analysis demonstrated a strong correlation with established markers of oligodendrocyte development, including myelin-associated genes (MOG, MBP) and key transcriptional regulators (PDGFRA, SOX5, SOX6, SOX11). THAP9 lacks homologues in mice, highlighting potential human-specific mechanisms in oligodendrocyte development and emphasising the importance of studying species-specific factors in neurodevelopment. Our findings suggest that THAP9 is a novel human-specific regulator of oligodendrocyte maturation and opens new avenues for studying myelination disorders.