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

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This preprint used integrative analyses of publicly available RNA-sequencing and H3K27ac ChIP-sequencing datasets from human oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes (MOs) to study THAP9, a human protein homologous to a Drosophila transposase whose oligodendrocyte function is unknown. THAP9 was found to be significantly upregulated during oligodendrocyte maturation, with co-expression strongly correlating with established oligodendrocyte developmental markers and regulators including MOG, MBP, PDGFRA, and SOX-family transcription factors. The authors note a key caveat that THAP9 lacks mouse homologues, limiting direct cross-species model validation and emphasizing potential human-specific regulatory mechanisms. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

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 publicly available 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.
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Integrative Genomic Analysis Identifies THAP9 as a Human-Specific Regulator of Oligodendrocyte Differentiation | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 9 August 2025 V1 Latest version Share on Integrative Genomic Analysis Identifies THAP9 as a Human-Specific Regulator of Oligodendrocyte Differentiation Authors : Tanuja Bhardwaj , Dhrumi Patel , and sharmistha MAJUMDAR 0000-0003-4356-7237 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.175477154.44810129/v1 Published Journal of Neurochemistry Version of record Peer review timeline 141 views 81 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract 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 publicly available 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. Supplementary Material File (main_text_images_oligo_manuscript.docx) Download 1.52 MB File (oligo_paper_manuscript.doc) Download 133.00 KB Information & Authors Information Version history V1 Version 1 09 August 2025 Peer review timeline Published Journal of Neurochemistry Version of Record 29 Jan 2026 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords oligodendrocyte maturation transcriptional regulation transposable elements Authors Affiliations Tanuja Bhardwaj Indian Institute of Technology Gandhinagar View all articles by this author Dhrumi Patel Indian Institute of Technology Gandhinagar View all articles by this author sharmistha MAJUMDAR 0000-0003-4356-7237 [email protected] Indian Institute of Technology Gandhinagar View all articles by this author Metrics & Citations Metrics Article Usage 141 views 81 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Tanuja Bhardwaj, Dhrumi Patel, sharmistha MAJUMDAR. Integrative Genomic Analysis Identifies THAP9 as a Human-Specific Regulator of Oligodendrocyte Differentiation. Authorea . 09 August 2025. DOI: https://doi.org/10.22541/au.175477154.44810129/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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