Divergent reprogramming routes lead to alternative stem-cell states

作者：Tonge Peter D; Corso Andrew J; Monetti Claudio; Hussein Samer M I; Puri Mira C; Michael Iacovos P; Li Mira; Lee Dong Sung; Mar Jessica C; Cloonan Nicole; Wood David L; Gauthier Maely E; Korn Othmar; Clancy Jennifer L; Preiss Thomas; Grimmond Sean M; Shin Jong Yeon; Seo Jeong Sun; Wells Christine A; Rogers Ian M; Nagy Andras^*

来源：Nature, 2014, 516(7530): 192-+.

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.

• 出版日期2014-12-11
• 单位河北医科大学