ArticleNature communications2023
OVOL2 sustains postnatal thymic epithelial cell identity.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 4 citations in OpenAlex.
- Autoimmune non-coding variants perturb transcription factor-cofactor complex assembly linked to enhancer activity.bioRxiv : the preprint server for biology · 2026Article
- Immune signaling as a determinant of cellular identity and tissue function.Frontiers in immunology · 2026Review
- Structural insights into the ubiquitin-independent midnolin-proteasome pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Stem cell expression of CXCR4 regulates tissue composition in the vomeronasal organ.Journal of cell science · 2025Article
- Viable mutations of mouse midnolin suppress B cell malignancies.The Journal of experimental medicine · 2024Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Distinct pathways and molecules may support embryonic versus postnatal thymic epithelial cell (TEC) development and maintenance. Here, we identify a mechanism by which TEC numbers and function are maintained postnatally. A viable missense allele (C120Y) of Ovol2, expressed ubiquitously or specifically in TECs, results in lymphopenia, in which T cell development is compromised by loss of medullary TECs and dysfunction of cortical TECs. We show that the epithelial identity of TECs is aberrantly subverted towards a mesenchymal state in OVOL2-deficient mice. We demonstrate that OVOL2 inhibits the epigenetic regulatory BRAF-HDAC complex, specifically disrupting RCOR1-LSD1 interaction. This causes inhibition of LSD1-mediated H3K4me2 demethylation, resulting in chromatin accessibility and transcriptional activation of epithelial genes. Thus, OVOL2 controls the epigenetic landscape of TECs to enforce TEC identity. The identification of a non-redundant postnatal mechanism for TEC maintenance offers an entry point to understanding thymic involution, which normally begins in early adulthood.
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Registered trials
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