Seymour Tracy, Twigger Alecia-Jane, Kakulas Foteini
School of Chemistry and Biochemistry, Faculty of Science, the University of Western Australia, Perth, Western Australia 6009, Australia.
School of Medicine and Pharmacology, Faculty of Medicine, Dentistry and Health Sciences, the University of Western Australia, Perth, Western Australia 6009, Australia.
Int J Mol Sci. 2015 Nov 13;16(11):27288-301. doi: 10.3390/ijms161126024.
Pluripotent stem cells (PSCs) attracted considerable interest with the successful isolation of embryonic stem cells (ESCs) from the inner cell mass of murine, primate and human embryos. Whilst it was initially thought that the only PSCs were ESCs, in more recent years cells with similar properties have been isolated from organs of the adult, including the breast and brain. Adult PSCs in these organs have been suggested to be remnants of embryonic development that facilitate normal tissue homeostasis during repair and regeneration. They share certain characteristics with ESCs, such as an inherent capacity to self-renew and differentiate into cells of the three germ layers, properties that are regulated by master pluripotency transcription factors (TFs) OCT4 (octamer-binding transcription factor 4), SOX2 (sex determining region Y-box 2), and homeobox protein NANOG. Aberrant expression of these TFs can be oncogenic resulting in heterogeneous tumours fueled by cancer stem cells (CSC), which are resistant to conventional treatments and are associated with tumour recurrence post-treatment. Further to enriching our understanding of the role of pluripotency TFs in normal tissue function, research now aims to develop optimized isolation and propagation methods for normal adult PSCs and CSCs for the purposes of regenerative medicine, developmental biology, and disease modeling aimed at targeted personalised cancer therapies.
随着从鼠类、灵长类和人类胚胎的内细胞团成功分离出胚胎干细胞(ESC),多能干细胞(PSC)引起了广泛关注。虽然最初认为唯一的PSC是ESC,但近年来已从包括乳腺和大脑在内的成体器官中分离出具有相似特性的细胞。这些器官中的成体PSC被认为是胚胎发育的残余物,在修复和再生过程中促进正常组织的稳态。它们与ESC具有某些共同特征,例如自我更新和分化为三个胚层细胞的内在能力,这些特性由多能性主转录因子(TF)OCT4(八聚体结合转录因子4)、SOX2(性别决定区Y盒2)和同源盒蛋白NANOG调节。这些TF的异常表达可能具有致癌性,导致由癌症干细胞(CSC)驱动的异质性肿瘤,这些肿瘤对传统治疗有抗性,并与治疗后的肿瘤复发相关。除了丰富我们对多能性TF在正常组织功能中作用的理解之外,现在的研究旨在为再生医学、发育生物学和旨在靶向个性化癌症治疗的疾病建模开发优化的正常成体PSC和CSC的分离和增殖方法。