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Epithelial cell adhesion molecule (EpCAM) complex proteins promote transcription factor-mediated pluripotency
Hsiang-Po Huang1, Pin-Hsun Chen, Chun-Ying Yu
1Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan.
The Journal of Biological Chemistry
|July 30, 2011
Summary
Epithelial cell adhesion molecule (EpCAM) and Cldn7 are crucial for reprogramming somatic cells into induced pluripotent stem cells (iPSCs). Enhancing EpCAM levels boosts reprogramming efficiency and generates functional iPSCs.
Area of Science:
- Stem Cell Biology
- Molecular Biology
- Cellular Reprogramming
Background:
- Epithelial cell adhesion molecule (EpCAM) is highly expressed in embryonic stem cells (ESCs) and implicated in pluripotency maintenance.
- The role of EpCAM and associated proteins in somatic cell reprogramming remains largely unexplored.
- EpCAM signaling pathways are known to be activated in epithelial cancer cells.
Purpose of the Study:
- To investigate the role of EpCAM and Cldn7 in somatic cell reprogramming.
- To determine if EpCAM signaling influences the efficiency of induced pluripotent stem cell (iPSC) generation.
- To elucidate the molecular mechanisms by which EpCAM affects reprogramming.
Main Methods:
- Quantitative RT-PCR to analyze gene expression (Oct4, Sox2, Klf4, c-Myc, EpCAM, Cldn7) in mouse embryonic fibroblasts (MEFs).
- Assays for alkaline phosphatase and Nanog positivity to assess reprogramming efficiency.
- Overexpression and inhibition studies of EpCAM and Cldn7, including the EpCAM intercellular domain (EpICD).
- Western blotting to evaluate p53 and p21 expression.
- Reporter assays to measure Oct4 promoter activity.
- In vitro and in vivo characterization of generated iPSCs.
Main Results:
- EpCAM and Cldn7 expression were upregulated during OSKM-mediated reprogramming of MEFs.
- Inhibition of EpCAM or Cldn7 impaired reprogramming efficiency.
- Overexpression of EpCAM, Cldn7, or EpICD significantly enhanced reprogramming efficiency.
- EpCAM and EpICD overexpression repressed p53 and p21 expression and activated Oct4 promoter activity.
- EpCAM-reprogrammed iPSCs displayed molecular and functional characteristics similar to mouse ESCs.
Conclusions:
- EpCAM and Cldn7 play critical roles in somatic cell reprogramming.
- EpCAM signaling enhances reprogramming efficiency, potentially by upregulating Oct4 and suppressing the p53-p21 pathway.
- EpCAM offers a promising strategy for more effective generation of induced pluripotent stem cells.
