Kulcenty Katarzyna, Wróblewska Joanna, Mazurek Sylwia, Liszewska Ewa, Jaworski Jacek
Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland ; Gene Therapy Laboratory, Department of Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
Gene Therapy Laboratory, Department of Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland ; Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.
Contemp Oncol (Pozn). 2015;19(1A):A22-9. doi: 10.5114/wo.2014.47134.
Growing knowledge concerning transcriptional control of cellular pluripotency has led to the discovery that the fate of differentiated cells can be reversed, which has resulted in the generation, by means of genetic manipulation, of induced pluripotent stem cells. Overexpression of just four pluripotency-related transcription factors, namely Oct3/4, Sox2, Klf4, and c-Myc (Yamanaka factors, OKSM), in fibroblasts appears sufficient to produce this new cell type. Currently, we know that these factors induce several changes in genetic program of differentiated cells that can be divided in two general phases: the initial one is stochastic, and the subsequent one is highly hierarchical and organised. This review briefly discusses the molecular events leading to induction of pluripotency in response to forced presence of OKSM factors in somatic cells. We also discuss other reprogramming strategies used thus far as well as the advantages and disadvantages of laboratory approaches towards pluripotency induction in different cell types.
关于细胞多能性转录调控的知识不断增长,促使人们发现分化细胞的命运可以逆转,这使得通过基因操作产生了诱导多能干细胞。在成纤维细胞中,仅过表达四种与多能性相关的转录因子,即Oct3/4、Sox2、Klf4和c-Myc(山中因子,OKSM),似乎就足以产生这种新的细胞类型。目前,我们知道这些因子会在分化细胞的基因程序中引发几种变化,这些变化可分为两个一般阶段:初始阶段是随机的,随后阶段是高度分层且有序的。本综述简要讨论了在体细胞中因强制存在OKSM因子而导致多能性诱导的分子事件。我们还讨论了迄今为止使用的其他重编程策略,以及在不同细胞类型中诱导多能性的实验室方法的优缺点。