FOXO4-SP6 axis controls surface epithelium commitment by mediating epigenomic remodeling.

IF 5.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Reports Pub Date : 2025-04-08 Epub Date: 2025-03-13 DOI:10.1016/j.stemcr.2025.102445

Jiafeng Liu, Huaxing Huang, Fengjiao An, Siqi Wu, Huizhen Guo, Bofeng Wang, Zhuo Han, Jieying Tan, Zesong Lin, Yihang Fang, Jinpeng Liu, Hanning Ye, Yuru Du, Kunlun Mo, Ying Huang, Mingsen Li, Li Wang, Zhen Mao, Hong Ouyang

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引用次数: 0

Abstract

Proper development of surface epithelium (SE) is a requisite for the normal development and function of ectodermal appendages; however, the molecular mechanisms underlying SE commitment remain largely unexplored. Here, we developed a KRT8 reporter system and utilized it to identify FOXO4 and SP6 as novel, essential regulators governing SE commitment. We found that the FOXO4-SP6 axis governs SE fate and its abrogation markedly impedes SE fate determination. Mechanistically, FOXO4 regulates SE initiation by shaping the SE chromatin accessibility landscape and regulating the deposition of H3K4me3. SP6, as a novel effector of FOXO4, activates SE-specific genes through modulating the H3K27ac deposition across their super-enhancers. Our work highlights the regulatory function of the FOXO4-SP6 axis in SE development, contributing to an improved understanding of SE fate decisions and providing a research foundation for the therapeutic application of ectodermal dysplasia.

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FOXO4-SP6轴通过介导表观基因组重塑来控制表面上皮的承诺。

表面上皮（SE）的正常发育是外胚层附属物正常发育和功能的必要条件；然而，SE承诺的分子机制在很大程度上仍未得到探索。在这里，我们开发了一种 KRT8 报告系统，并利用它鉴定出 FOXO4 和 SP6 是调控 SE 承诺的新型重要调控因子。我们发现，FOXO4-SP6轴调控着SE的命运，削弱该轴会明显阻碍SE命运的决定。从机制上讲，FOXO4 通过塑造 SE 染色质可及性景观和调节 H3K4me3 的沉积来调节 SE 的启动。SP6作为FOXO4的新型效应因子，通过调节超级增强子上的H3K27ac沉积激活SE特异性基因。我们的研究突出了FOXO4-SP6轴在SE发育过程中的调控功能，有助于加深对SE命运决定的理解，并为外胚层发育不良的治疗应用提供了研究基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.