TGF beta signaling regulates the choice between pluripotent and neural fates during reprogramming of human urine derived cells

作者：Wang Lihui; Li Xirui; Huang Wenhao; Zhou Tiancheng; Wang Haitao; Lin Aiping; Hutchins Andrew Paul; Su Zhenghui; Chen Qianyu; Pei Duanqing; Pan Guangjin^*

来源：Scientific Reports, 2016, 6: 22484.

DOI：10.1038/srep22484

Human urine cells (HUCs) can be reprogrammed into neural progenitor cells (NPCs) or induced pluripotent stem cells (iPSCs) with defined factors and a small molecule cocktail, but the underlying fate choice remains unresolved. Here, through sequential removal of individual compound from small molecule cocktail, we showed that A8301, a TGF beta signaling inhibitor, is sufficient to switch the cell fate from iPSCs into NPCs in OSKM-mediated HUCs reprogramming. However, TGF beta exposure at early stage inhibits HUCs reprogramming by promoting EMT. Base on these data, we developed an optimized approach for generation of NPCs or iPSCs from HUCs with significantly improved efficiency by regulating TGF beta activity at different reprogramming stages. This approach provides a simplified and improved way for HUCs reprogramming, thus would be valuable for banking human iPSCs or NPCs from people with different genetic background.

• 单位
  中国科学院; 大连医科大学1