Brevini T A L, Pennarossa G, Manzoni E F M, Gandolfi C E, Zenobi A, Gandolfi F
Laboratory of Biomedical Embryology, Unistem, Università degli Studi di Milano, Via Celoria 10, 20133 Milan, Italy.
Clin Epigenetics. 2016 Nov 16;8:119. doi: 10.1186/s13148-016-0283-5. eCollection 2016.
In the presence of different environmental cues that are able to trigger specific responses, a given genotype has the ability to originate a variety of different phenotypes. This property is defined as plasticity and allows cell fate definition and tissue specialization. Fundamental epigenetic mechanisms drive these modifications in gene expression and include DNA methylation, histone modifications, chromatin remodeling, and microRNAs. Understanding these mechanisms can provide powerful tools to switch cell phenotype and implement cell therapy. Environmentally influenced epigenetic changes have also been associated to many diseases such as cancer and neurodegenerative disorders, with patients that do not respond, or only poorly respond, to conventional therapy. It is clear that disorders based on an individual's personal genomic/epigenomic profile can rarely be successfully treated with standard therapies due to genetic heterogeneity and epigenetic alterations and a personalized medicine approach is far more appropriate to manage these patients. We here discuss the recent advances in small molecule approaches for personalized medicine, drug targeting, and generation of new cells for medical application. We also provide prospective views of the possibility to directly convert one cell type into another, in a safe and robust way, for cell-based clinical trials and regenerative medicine.
在能够触发特定反应的不同环境线索存在的情况下，给定的基因型有能力产生多种不同的表型。这种特性被定义为可塑性，并允许细胞命运的确定和组织特化。基本的表观遗传机制驱动基因表达的这些修饰，包括DNA甲基化、组蛋白修饰、染色质重塑和微小RNA。了解这些机制可以提供强大的工具来转换细胞表型并实施细胞治疗。受环境影响的表观遗传变化也与许多疾病相关，如癌症和神经退行性疾病，这些疾病的患者对传统治疗无反应或反应不佳。显然，基于个体的个人基因组/表观基因组特征的疾病很少能用标准疗法成功治疗，因为存在遗传异质性和表观遗传改变，个性化医疗方法更适合管理这些患者。我们在此讨论小分子方法在个性化医疗、药物靶向以及用于医学应用的新细胞生成方面的最新进展。我们还展望了以安全、可靠的方式直接将一种细胞类型转化为另一种细胞类型用于基于细胞的临床试验和再生医学的可能性。
