Authors: Jian Shu*, Chen Wu*, Yetao Wu*, Zhiyuan Li*, Sida Shao, Wenhui Zhao, Xing Tang, Huan Yang, Lijun Shen, XiaohanZuo, Weifeng Yang, Yan Shi, Xiaochun Chi, Hongquan Zhang, Ge Gao, Youmin Shu, Kehu Yuan, Weiwu He, Chao Tang, Yang Zhao, Hongkui Deng.
Journal: CELL
DOI: 10.1016/j.cell.2013.05.001
Link: https://doi.org/10.1016/j.cell.2013.05.001
Published: MAY 23 2013
Document Type: Article
Abstract:
The reprogramming factors that induce pluripotency have been identified primarily from embryonic stem cell (ESC)-enriched, pluripotency-associated factors. Here, we report that, during mouse somatic cell reprogramming, pluripotency can be induced with lineage specifiers that are pluripotency rivals to suppress ESC identity, most of which are not enriched in ESCs. We found that OCT4 and SOX2, the core regulators of pluripotency, can be replaced by lineage specifiers that are involved in mesendo-dermal (ME) specification and in ectodermal (ECT) specification, respectively. OCT4 and its substitutes attenuated the elevated expression of a group of ECT genes, whereas SOX2 and its substitutes curtailed a group of ME genes during reprogramming. Surprisingly, the two counteracting lineage specifiers can synergistically induce pluripotency in the absence of both OCT4 and SOX2. Our study suggests a "seesaw model'' in which a balance that is established using pluripotency factors and/or counteracting lineage specifiers can facilitate reprogramming.
Keywords:
EMBRYONIC STEM-CELLS; PRIMITIVE ENDODERM; DIRECT CONVERSION; HUMAN FIBROBLASTS; DIFFERENTIATION; OCT4; EXPRESSION; GENERATION; GENE; DEDIFFERENTIATION