期刊
STEM CELLS AND DEVELOPMENT
卷 30, 期 21, 页码 1082-1091出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2021.0185
关键词
human embryonic stem cells; MUC1-C; proliferation; ROS; glycolysis; reprogramming
资金
- National Research Foundation (NRF) of Korea - Ministry of Science and ICT [2017M3A9B4065302, 2021R1A2C1006767]
- Basic Science Research Program through the NRF - Ministry of Education [2019R1A6A3A01092179]
- National Research Foundation of Korea [2021R1A2C1006767, 2019R1A6A3A01092179, 2017M3A9B4065302] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The study revealed that MUC1-C is expressed in human ES cells and is crucial for cell proliferation, maintenance of pluripotency, optimal ROS levels, and high glycolytic flux. The inhibition of MUC1-C resulted in reduced proliferative capacity and promotion of cell death in human ES cells, while overexpression of MUC1-C enhanced reprogramming efficiency to induced pluripotent stem cells from fibroblast cells.
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.
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