MUC1-C Contributes to the Maintenance of Human Embryonic Stem Cells and Promotes Somatic Cell Reprogramming.

Abstract

Mucin 1 (MUC1) is a transmembrane glycoprotein overexpressed in several cancer cells in which it regulates cell surface properties, tumor invasion, and cell death. Recently, we reported that MUC1-C, the C-terminal subunit of MUC1, is involved in the growth of mouse embryonic stem (ES) cells. However, the functional significance of MUC1-C in human ES cells remains unclear. In this study, we investigated the expression and function of MUC1-C in human ES cells. Based on reverse transcription-polymerase chain reaction, western blotting, and confocal microscopy following immunostaining, undifferentiated human ES cells expressed MUC1-C and the expression level decreased during differentiation. Inhibition of MUC1-C, by the peptide inhibitor GO201 that targets the cytoplasmic domain of MUC1-C (MUC1-CD), reduced cell proliferation and OCT4 protein expression, and promoted cell death. Moreover, the inhibition of MUC1-C increased the intracellular reactive oxygen species (ROS) levels and downregulated expression of glycolysis-related enzymes. These findings indicate that expression and function of MUC1-C are required for stem cell properties involved in cell proliferation, maintenance of pluripotency and optimal ROS levels, and a high glycolytic flux in human ES cells. In addition, forced overexpression of MUC1-CD increased the efficiency of reprogramming from fibroblast cells to induced pluripotent stem cells, suggesting that MUC1-C expression can contribute to the reprogramming process.