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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Cells, Cultured
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Cellular Reprogramming*
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Epithelial Cell Adhesion Molecule / chemistry
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Epithelial Cell Adhesion Molecule / genetics
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Epithelial Cell Adhesion Molecule / metabolism*
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Induced Pluripotent Stem Cells / cytology
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Induced Pluripotent Stem Cells / metabolism*
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Kruppel-Like Factor 4
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Kruppel-Like Transcription Factors / genetics*
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Kruppel-Like Transcription Factors / metabolism
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Mice
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Mice, Inbred C57BL
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Octamer Transcription Factor-3 / genetics*
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Octamer Transcription Factor-3 / metabolism
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Protein Domains
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Epithelial Cell Adhesion Molecule
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Klf4 protein, mouse
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Kruppel-Like Factor 4
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Kruppel-Like Transcription Factors
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Octamer Transcription Factor-3
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Pou5f1 protein, mouse
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STAT3 Transcription Factor
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endothelial PAS domain-containing protein 1