Kelly Gregory M, Gatie Mohamed I
Department of Biology, Molecular Genetics Unit, Western University, London, ON, Canada; Collaborative Program in Developmental Biology, Western University, London, ON, Canada; Department of Paediatrics and Department of Physiology and Pharmacology, Western University, London, ON, Canada; Child Health Research Institute, London, ON, Canada; Ontario Institute for Regenerative Medicine, Toronto, ON, Canada; The Hospital for Sick Children, Toronto, ON, Canada.
Department of Biology, Molecular Genetics Unit, Western University, London, ON, Canada; Collaborative Program in Developmental Biology, Western University, London, ON, Canada.
Stem Cells Int. 2017;2017:3684178. doi: 10.1155/2017/3684178. Epub 2017 Mar 8.
Just over ten years have passed since the seminal Takahashi-Yamanaka paper, and while most attention nowadays is on induced, embryonic, and cancer stem cells, much of the pioneering work arose from studies with embryonal carcinoma cells (ECCs) derived from teratocarcinomas. This original work was broad in scope, but eventually led the way for us to focus on the components involved in the gene regulation of stemness and differentiation. As the name implies, ECCs are malignant in nature, yet maintain the ability to differentiate into the 3 germ layers and extraembryonic tissues, as well as behave normally when reintroduced into a healthy blastocyst. Retinoic acid signaling has been thoroughly interrogated in ECCs, especially in the F9 and P19 murine cell models, and while we have touched on this aspect, this review purposely highlights how some key transcription factors regulate pluripotency and cell stemness prior to this signaling. Another major focus is on the epigenetic regulation of ECCs and stem cells, and, towards that end, this review closes on what we see as a new frontier in combating aging and human disease, namely, how cellular metabolism shapes the epigenetic landscape and hence the pluripotency of all stem cells.
自高桥和山中的开创性论文发表以来，已经过去了十多年。如今，大多数关注都集中在诱导多能干细胞、胚胎干细胞和癌症干细胞上，但许多开创性工作都源于对源自畸胎癌的胚胎癌细胞（ECCs）的研究。这项最初的工作范围广泛，但最终为我们专注于干细胞干性和分化的基因调控所涉及的成分指明了方向。顾名思义，ECCs本质上是恶性的，但仍保持分化为三个胚层和胚外组织的能力，并且当重新引入健康囊胚时表现正常。维甲酸信号通路已在ECCs中得到深入研究，特别是在F9和P19小鼠细胞模型中，虽然我们已经涉及到这方面，但本综述特意强调了一些关键转录因子在该信号传导之前如何调节多能性和细胞干性。另一个主要重点是ECCs和干细胞的表观遗传调控，为此，本综述以我们视为对抗衰老和人类疾病的一个新前沿的内容作为结尾，即细胞代谢如何塑造表观遗传格局，进而影响所有干细胞的多能性。
