Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada [2] Institute of Medical Science, University of Toronto, Toronto, Ontario M5T 3H7, Canada.
Nature. 2014 Dec 11;516(7530):192-7. doi: 10.1038/nature14047.
Pluripotency is defined by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluripotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluripotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique epigenetic modifications to arrive at a stable, Nanog-positive, alternative pluripotent state. In doing so, we prove that the pluripotent spectrum can encompass multiple, unique cell states.
多能性是指细胞分化为三个胚胎胚层（外胚层、中胚层和内胚层）衍生物的能力。多能细胞可以通过胚胎干细胞的典型分化或体细胞重编程获得。通过强制表达关键转录因子，体细胞被诱导获得多能干细胞（iPSC）状态，并且在小鼠中，这些细胞可以通过生成完全由 iPSC 衍生的胚胎和小鼠来满足多能细胞最严格的所有发育测定。然而，目前尚不清楚是否存在其他类别的多能细胞，或者重编程表型的范围包括哪些。在这里，我们通过完全表征独立于 iPSC 状态的预先定义的重编程细胞，探索体细胞重编程的替代结果。我们证明，通过维持升高的重编程因子表达水平，小鼠胚胎成纤维细胞经历独特的表观遗传修饰，从而达到稳定的、Nanog 阳性的、替代性多能状态。这样，我们证明了多潜能谱可以包含多个独特的细胞状态。
