整合多组学数据的小鼠梅克尔软骨的表观遗传特征分析

doi:10.19439/j.sjos.2026.02.001

上海口腔医学 ›› 2026, Vol. 35 ›› Issue (2): 113-120.doi: 10.19439/j.sjos.2026.02.001

整合多组学数据的小鼠梅克尔软骨的表观遗传特征分析

潘祉源^1,*, 王宏伟^1,*, 程理¹, 林国芬^2#, 代杰文^1#

1.上海交通大学医学院附属第九人民医院口腔颅颌面科,上海交通大学口腔医学院,国家口腔医学中心,口腔疾病国家临床医学研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所,上海 200011;
2.浙江大学医学院附属口腔医院,浙江省口腔疾病临床医学研究中心,浙江省口腔生物医学研究重点实验室,浙江大学癌症研究院,口腔生物材料与器械浙江省工程研究中心,浙江杭州 310000

收稿日期:2025-02-24 修回日期:2025-04-21 出版日期:2026-04-25 发布日期:2026-04-27
通讯作者: 代杰文,E-mail:daijiewen@163.com;林国芬,E-mail:ashley0109@zju.edu.cn。^#共同通信作者
作者简介:潘祉源（2000—）,男,在读硕士研究生,E-mail:15524800594@163.com;王宏伟（1988—）,女,主治医师,E-mail:xnngo-go@163.com。^*并列第一作者
基金资助:
国家自然科学基金（82071097,82370906）; 浙江省口腔生物医学研究重点实验室基金项目（2021M007）; 上海市卫生健康委员会卓越项目(20234Z0006); 上海交通大学医学院“双百人”研究型医师资助项目（20240810）

Analysis of epigenetic features of mouse Meckel’s cartilage by integrating multi-omics data

Pan Zhiyuan¹, Wang Hongwei¹, Cheng Li¹, Lin Guofen², Dai Jiewen¹

1. Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology. Shanghai 200011;
2. Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province. Hangzhou 310000, Zhejiang Province, China

Received:2025-02-24 Revised:2025-04-21 Online:2026-04-25 Published:2026-04-27

摘要/Abstract

摘要： 目的:基于多组学数据,探讨小鼠梅克尔软骨的表观遗传修饰特征及其潜在的基因表达调控机制。方法:从GEO数据库中收集已发布的多种小鼠软骨细胞数据集,以及本课题组先前发布的E14.5梅克尔软骨及E14.5前肢软骨多组学数据。利用生物信息学手段,比较不同软骨细胞样本间的染色质开放性、组蛋白乙酰化修饰和三维基因组结构差异。结果:ATAC-seq分析结果表明,E14.5梅克尔软骨与增殖延伸阶段的长骨端软骨具有更相近的染色质开放模式。CUT&Tag分析结果显示,总计11 899个染色质区域的H3K27ac修饰水平在梅克尔软骨与前肢软骨之间存在显著差异,其中,8 572个区域的乙酰化修饰水平在梅克尔软骨中上调。Motif分析显示,在梅克尔软骨中上调的H3K27ac峰富集了大量Fos、Atf3、AP-1结合位点。整合分析CUT&Tag、Hi-C结果表明,在Runx2、Six2等基因座存在染色质环介导的启动子-超级增强子互作。结论:E14.5梅克尔软骨主要表现增殖性软骨细胞的染色质可及性特征。Fos、Six2等转录因子在梅克尔软骨增殖期的转录调控中可能发挥重要作用。与梅克尔软骨肥大相关的染色质表观遗传修饰变化,可能在梅克尔软骨的发育过程中逐渐出现。

关键词: 梅克尔软骨, 表观遗传学, 三维基因组, 下颌骨发育, 颅颌面外科学

Abstract: PURPOSE: To characterize the epigenetic features of mouse Meckel's cartilage and potential gene expression regulation mechanisms based on multi-omics data. METHODS: E14.5 Meckel's cartilage and forelimb cartilage multi-omics data in our group were incorporated, and published datasets of a wide range of mouse chondrocytes from the GEO database were also downloaded. Bioinformatics methods were used to compare chromatin accessibility, histone acetylation modifications, as well as three-dimensional genomic structural differences between different chondrocyte samples. Results: ATAC-seq analysis results showed that E14.5 Meckel's cartilage exhibited a more similar chromatin accessibility pattern to epiphyseal cartilage. CUT&Tag analysis results showed that H3K27ac modification level of 11 899 peaks differed significantly between Meckel's cartilage and forelimb cartilage, and acetylation modifications in 8 572 peaks were upregulated in Merkel's cartilage. Motif analysis results showed that the up-regulated H3K27ac peaks in Meckel's cartilage were enriched with Fos, Atf3, and AP-1 binding sites. Integration analysis of CUT&Tag and Hi-C results indicated the presence of chromatin loop-mediated promoter-super-enhancer interactions at the loci of Runx2 and Six2. CONCLUSIONS: E14.5 Meckel's cartilage mainly exhibits chromatin accessibility characteristics of proliferative chondrocytes. Transcription factors such as Fos, and Six2 may play an important role in the transcriptional regulation of Meckel's cartilage development during the proliferative stage. Changes in chromatin epigenetic modifications associated with hypertrophy of Meckel's cartilage may appear gradually during the later stage of Merkel's cartilage development.

Key words: Meckel's cartilage, Epigenetics, 3D-Genomics, mandibular development, Craniomaxillofacial surgery

中图分类号:

R782.6

潘祉源, 王宏伟, 程理, 林国芬, 代杰文. 整合多组学数据的小鼠梅克尔软骨的表观遗传特征分析[J]. 上海口腔医学, 2026, 35(2): 113-120.

Pan Zhiyuan, Wang Hongwei, Cheng Li, Lin Guofen, Dai Jiewen. Analysis of epigenetic features of mouse Meckel’s cartilage by integrating multi-omics data[J]. Shanghai Journal of Stomatology, 2026, 35(2): 113-120.

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整合多组学数据的小鼠梅克尔软骨的表观遗传特征分析

Analysis of epigenetic features of mouse Meckel’s cartilage by integrating multi-omics data

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