1. EpEX/EpCAM and Oct4 or Klf4 alone are sufficient to generate induced pluripotent stem cells through STAT3 and HIF2α
- Author
-
I.-I. Kuan, Shang-Chih Yang, Ting-Wen Kuo, Yaa-Jyuhn James Meir, Yi Ping Wang, Sareina Chiung-Yuan Wu, Han-Chung Wu, Jean Lu, and Kang-Hao Liang
- Subjects
0301 basic medicine ,STAT3 Transcription Factor ,Induced Pluripotent Stem Cells ,Kruppel-Like Transcription Factors ,Stem cell marker ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Kruppel-Like Factor 4 ,Mice ,SOX2 ,Protein Domains ,Basic Helix-Loop-Helix Transcription Factors ,Animals ,STAT3 ,Induced pluripotent stem cell ,Cells, Cultured ,Multidisciplinary ,biology ,Chemistry ,Epithelial cell adhesion molecule ,Cellular Reprogramming ,Epithelial Cell Adhesion Molecule ,Transmembrane protein ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,KLF4 ,biology.protein ,Reprogramming ,Octamer Transcription Factor-3 - Abstract
Epithelial cell adhesion molecule (EpCAM) was reported to be cleaved into extracellular domain of EpCAM (EpEX) and intracellular domain of EpCAM (EpICD). We previously reported that EpCAM serves as a potent stem cell marker which is highly and selectively expressed by undifferentiated rather than differentiated hESC. However, the functional role of EpCAM remains elusive. Here, we found that EpEX and EpCAM enhance the efficiency of OSKM reprogramming. Interestingly, Oct4 or Klf4 alone, but not Sox2, can successfully reprogram fibroblasts into iPSCs with EpEX and EpCAM. Moreover, EpEX and EpCAM trigger reprogramming via activation of STAT3, which leads to the nuclear-translocation of HIF2α. This study reveals the importance of a novel EpEX/EpCAM-STAT3-HIF2α signal in the reprogramming process, and uncovers a new means of triggering reprogramming by delivery of soluble and transmembrane proteins.
- Published
- 2017
- Full Text
- View/download PDF