Crotonate enhances intestinal regeneration after injury via HBO1-mediated H3K14 crotonylation.

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-10-02 DOI:10.1038/s41467-025-63869-2

Yanhui Xiao,Shicheng Yu,Mengxian Zhang,Nanshan Zhong,Shan Hua,Zhi Fang,Zhe Zhang,Huidong Liu,Ronghui Tan,Yuan Liu,Ye-Guang Chen

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引用次数: 0

Abstract

The intestinal epithelium undergoes rapid turnover driven by Lgr5+ intestinal stem cells at the crypt base, and can recover upon damage. Histone crotonylation plays a critical role in chromatin regulation and gene expression. However, the role of histone crotonylation, specifically H3K14 crotonylation (H3K14cr) in the intestine remains poorly understood. Here we demonstrate that both crotonate and H3K14cr levels are increased in the regenerating crypts. Treatment with sodium crotonate significantly alleviates dextran sulfate sodium induced colitis, an effect largely dependent on HBO1-mediated H3K14cr. Notably, HBO1 deficiency severely dampens regeneration, correlating with reduced H3K14ac and H3K14cr levels, decreased chromatin accessibility at transcriptional start sites, and impaired expression of stem and fetal genes. Single-cell RNA sequencing analysis reveals that HBO1 is expressed in stem cells and regenerative cells during recovery after irradiation, further supporting the critical role of HBO1 in intestinal regeneration. Together, our findings uncover a mechanism by which crotonate, HBO1, and H3K14cr contribute to epithelial regeneration and suggest that crotonate may represent a promising therapeutic agent for the treatment of gastrointestinal diseases.

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Crotonate通过hbo1介导的H3K14 crotonylation促进损伤后肠道再生。

肠上皮在隐窝基部的Lgr5+肠干细胞的驱动下进行快速更新，并可在损伤后恢复。组蛋白巴豆酰化在染色质调控和基因表达中起着关键作用。然而，组蛋白巴豆酰化，特别是H3K14巴豆酰化（H3K14cr）在肠道中的作用仍然知之甚少。本研究表明，在再生的隐窝中，crotonate和H3K14cr水平均升高。巴豆酸钠治疗可显著缓解葡聚糖硫酸钠诱导的结肠炎，其作用主要依赖于hbo1介导的H3K14cr。值得注意的是，HBO1缺乏严重抑制再生，与H3K14ac和H3K14cr水平降低、转录起始位点染色质可及性降低以及干细胞和胎儿基因表达受损相关。单细胞RNA测序分析显示，HBO1在辐照后恢复的干细胞和再生细胞中表达，进一步支持了HBO1在肠道再生中的关键作用。总之，我们的研究结果揭示了巴豆酸盐、HBO1和H3K14cr促进上皮再生的机制，并表明巴豆酸盐可能是治疗胃肠道疾病的一种有前途的治疗剂。

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

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.