OVOL2 sustains postnatal thymic epithelial cell identity.
OVOL2 sustains postnatal thymic epithelial cell identity.
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DOI：
10.1038/s41467-023-43456-z
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发表时间：
2023-11-27
影响因子：
16.6
通讯作者：
Beutler, Bruce
中科院分区：
文献类型：
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作者：
Zhong, Xue;Peddada, Nagesh;Wang, Jianhui;Moresco, James J;Zhan, Xiaowei;Shelton, John M;SoRelle, Jeffrey A;Keller, Katie;Lazaro, Danielle Renee;Moresco, Eva Marie Y;Choi, Jin Huk;Beutler, Bruce
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. The molecular mechanisms that maintain thymic epithelial cell (TEC) identity throughout life are incompletely understood. Here, the authors demonstrate that the transcription factor, Ovol2, maintains post-natal TECs by preventing their epithelial-to-mesenchymal transition.
胸腺上皮细胞发育及其在人类疾病中的功能障碍
影响因子：
--
作者：
Sun L;Li H;Luo H;Zhao Y
通讯作者：
Zhao Y