Skirball Institute of Biomolecular Medicine, Department of Cell Biology and Helen L. and Martin S. Kimmel Center for Biology and Medicine, NYU School of Medicine, New York, NY 10016, USA.
Edward and Sandra Meyer Cancer Center and Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
Cell Rep. 2018 Jan 23;22(4):876-884. doi: 10.1016/j.celrep.2017.12.098. Epub 2018 Jan 28.
The ability of induced pluripotent stem cells (iPSCs) to differentiate into all adult cell types makes them attractive for research and regenerative medicine; however, it remains unknown when and how this capacity is established. We characterized the acquisition of developmental pluripotency in a suitable reprogramming system to show that iPSCs prior to passaging become capable of generating all tissues upon injection into preimplantation embryos. The developmental potential of nascent iPSCs is comparable to or even surpasses that of established pluripotent cells. Further functional assays and genome-wide molecular analyses suggest that cells acquiring developmental pluripotency exhibit a unique combination of properties that distinguish them from canonical naive and primed pluripotency states. These include reduced clonal self-renewal potential and the elevated expression of differentiation-associated transcriptional regulators. Our observations close a gap in the understanding of induced pluripotency and provide an improved roadmap of cellular reprogramming with ramifications for the use of iPSCs.
诱导多能干细胞（iPSCs）能够分化为所有成体细胞类型，这使它们成为研究和再生医学的理想选择；然而，目前尚不清楚这种能力是何时以及如何建立的。我们对合适的重编程系统中的多能性获得进行了特征描述，以表明在传代之前，iPSCs 能够在注射到着床前胚胎中时生成所有组织。新生 iPSCs 的发育潜能可与已建立的多能细胞相媲美，甚至超过后者。进一步的功能测定和全基因组分子分析表明，获得多能性的细胞表现出独特的组合特性，使其与经典的原始和初始多能性状态区分开来。这些特性包括降低的克隆自我更新潜力和分化相关转录调节因子的高表达。我们的观察结果填补了对诱导多能性理解的空白，并为细胞重编程提供了改进的路线图，对 iPSCs 的应用具有重要意义。
