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EpEX/EpCAM and Oct4 or Klf4 alone are sufficient to generate induced pluripotent stem cells through STAT3 and HIF2α. | LitMetric

AI Article Synopsis

  • Epithelial cell adhesion molecule (EpCAM) can be cleaved into two parts: the extracellular domain (EpEX) and the intracellular domain (EpICD), which play roles in stem cell biology.
  • The study shows that both EpEX and EpCAM improve the efficiency of reprogramming fibroblasts into induced pluripotent stem cells (iPSCs) when combined with specific factors like Oct4 and Klf4, highlighting their functional significance.
  • The mechanism involves the activation of a signaling pathway (STAT3) that leads to the movement of HIF2α into the nucleus, suggesting a novel way to enhance stem cell reprogramming through proteins like EpEX and EpCAM.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291097PMC
http://dx.doi.org/10.1038/srep41852DOI Listing

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