Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-ba...Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.展开更多
基金supported by the National Institute of Dental and Craniofacial Research grants, K08DE024603-02, DE019412, and DE01651a grant from 111 Project of MOE, Chinasupported by Open Fund of State Key Laboratory of Oral Diseases, Sichuan University
文摘Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.
文摘目的探讨19个组蛋白赖氨酸去甲基化酶(KDMs)在膀胱癌多组学中的表达模式与潜在作用。方法本研究使用UALCAN和GSCALite分析来自TCGA的膀胱癌样本的KDMs的转录表达和甲基化水平、体细胞变异多组学高通量测序数据。使用Kaplan Meier-Plotter和Assistant for clinical bioinformatics探讨KDMs的表达对BLCA样本的预后影响。利用Timer和GSCALite分析KDMs在膀胱癌中的免疫浸润和药物敏感性。结果分析结果首先揭示了KDMs在膀胱癌多组学中的表达特征,并不是所有KDMs都具有一致的表达模式。转录组数据分析显示KDM1A/1B/2B/4A/4B/5B/5C的表达上调(P<0.05),而KDM3B/6B/7C的表达下调。甲基化水平差异分析显示KDM1A/3B/4A/4B/4C/5A/5B/5C/7B的甲基化水平下调,而KDM7C甲基化水平上调(P<0.05)。相关性分析显示,14个KDMs家族成员的转录水平与甲基化水平呈负相关,其中KDM1A最显著。突变分析显示,KDM6A非同义突变频率最高,突变种类最多,且与其它KDMs的非同义突变具有互补性。生存分析显示,KDM3A/4C/5D/6A/7B对BLCA患者总生存率具有保护性作用,而KDM3B/5B/5C对BLCA患者无复发生存率具有危险性影响。综合预后模型证实KDM4C/6A/7B具有膀胱癌预后生物标志物的潜在作用,其表达与BLCA患者免疫浸润呈正相关。药物敏感性分析显示,KDM2B/3B/4B/4C/5A与大多数抗癌药物呈负相关,而KDM2B/4B与6种抗癌药物呈正相关(P<0.05)。结论本研究系统性地揭示了KDMs基因家族在膀胱癌中的高突变互补性、过表达与低甲基化负相关性的特征,并与膀胱癌预后、免疫浸润和药物敏感性密切相关。
