Schneider T A, Fishman V S, Liskovykh M A, Ponamartsev S V, Serov O L, Tomilin A N, Alenina N
Tsitologiia. 2014;56(12):869-80.
An adult mammal is composed of more than 200 different types of specialized somatic cells whose differentiated state remains stable over the life of the organism. For a long time it was believed that the differentiation process is irreversible, and the transition between the two types of specialized cells is impossible. The possibility of direct conversion of one differentiated cell type to another was first shown in the 80s of the last century in experiments on the conversion of fibroblasts into myoblasts by ectopic expression of the transcription factor MyoD. Surprisingly, this technology has remained unclaimed in cell biology for a long time. Interest in it revived after 200 thanks to the research of Novel Prize winner Shinya Yamanaka who has shown that a small set of transcription factors (Oct4, Sox2, Klf4 and c-Myc) is capable of restoring pluripotency in somatic cells which they lost in the process of differentiation. In 2010, using a similar strategy and the tissue-specific transcription factors Vierbuchen and coauthors showed the possibility of direct conversion of fibroblasts into neurons, i. e. the possibility of transdifferentiation of one type of somatic cells in the other. The works of these authoras were a breakthrough in the field of cell biology and gave a powerful impulse to the development of cell technologies for the needs of regenerative medicine. The present review discusses the main historical discoveries that preceded this work, evaluates the status of the problem and the progress in the development of methods for reprogramming at the moment, describes the main approaches to solving the problems of reprogramming of somatic cells into neuronal, and briefly discusses the prospect of application of reprogramming and transdifferentiation of cells for such important application areas as regenerative medicine, cell replacement therapy and drug screening.
成年哺乳动物由200多种不同类型的特化体细胞组成,其分化状态在生物体的生命周期中保持稳定。长期以来,人们一直认为分化过程是不可逆的,两种特化细胞类型之间的转变是不可能的。上世纪80年代,通过异位表达转录因子MyoD将成纤维细胞转化为成肌细胞的实验首次证明了一种分化细胞类型直接转化为另一种分化细胞类型的可能性。令人惊讶的是,这项技术在细胞生物学领域长期无人问津。由于诺贝尔奖获得者山中伸弥的研究,2000年后人们对它的兴趣重新燃起。山中伸弥的研究表明,一小部分转录因子(Oct4、Sox2、Klf4和c-Myc)能够恢复体细胞在分化过程中失去的多能性。2010年,Vierbuchen及其合作者采用类似策略,利用组织特异性转录因子证明了成纤维细胞直接转化为神经元的可能性,即一种体细胞类型向另一种体细胞类型转分化的可能性。这些作者的工作是细胞生物学领域的一项突破,为满足再生医学需求的细胞技术发展提供了强大动力。本综述讨论了这项工作之前的主要历史发现,评估了该问题的现状以及目前重编程方法的发展进展,描述了将体细胞重编程为神经元的主要方法,并简要讨论了细胞重编程和转分化在再生医学、细胞替代疗法和药物筛选等重要应用领域的应用前景。