Center for Regenerative Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
Cell Stem Cell. 2010 Jun 4;6(6):535-46. doi: 10.1016/j.stem.2010.05.003.
Murine pluripotent stem cells can exist in two functionally distinct states, LIF-dependent embryonic stem cells (ESCs) and bFGF-dependent epiblast stem cells (EpiSCs). However, human pluripotent cells so far seemed to assume only an epiblast-like state. Here we demonstrate that human iPSC reprogramming in the presence of LIF yields human stem cells that display morphological, molecular, and functional properties of murine ESCs. We termed these hLR5 iPSCs because they require the expression of five ectopic reprogramming factors, Oct4, Sox2, Klf4, cMyc, and Nanog, to maintain this more naive state. The cells are "metastable" and upon ectopic factor withdrawal they revert to standard human iPSCs. Finally, we demonstrate that the hLR5 state facilitates gene targeting, and as such provides a powerful tool for the generation of recombinant human pluripotent stem cell lines.
鼠多能干细胞可以存在于两种功能不同的状态，LIF 依赖性胚胎干细胞（ESCs）和 bFGF 依赖性胚外干细胞（EpiSCs）。然而，人类多能细胞迄今为止似乎只呈现出类胚外干细胞状态。在这里，我们证明了在 LIF 的存在下，人类 iPSC 的重编程产生了显示出形态、分子和功能特性的人类 ESCs 的人类干细胞。我们将这些 hLR5 iPSCs 称为因为它们需要表达五个外源性重编程因子，Oct4、Sox2、Klf4、cMyc 和 Nanog，以维持这种更原始的状态。这些细胞是“亚稳定的”，在异位因子撤回后，它们会恢复为标准的人类 iPSCs。最后，我们证明了 hLR5 状态有利于基因靶向，因此为生成重组人类多能干细胞系提供了强大的工具。
