Abstract
Accurate markers and molecular mechanisms of stem cell dormancy and activation are poorly understood. In this study, the anti-cancer drug, 5-fluorouracil, was used to selectively kill proliferating cells of human bronchial epithelial (HBE) cell line. This method can enrich and purify stem cell population. The dormant versus active status of stem cells was determined by phosphorylation of RNAp II Ser2. The surviving stem cells were cultured to form stem cell spheres expressing stem cell markers and transplanted into nude mice to form a teratoma. The results demonstrated the properties of stem cells and potential for multi-directional differentiation. Bisulfite sequencing polymerase chain reaction showed that demethylation of the Sox2 promoter by 5-FU resulted in Sox2 expression in the dormant stem cells. This study shows that the dormancy and activation of HBE stem cells is closely related to epigenetic modification.
Highlights
Adult stem cells in the body are generally in a state of dormancy or the G0 phase of the cell cycle
This study shows that the dormancy and activation of human bronchial epithelial (HBE) stem cells is closely related to epigenetic modification
The results of this study demonstrated a new method of inducing stem cells without gene transduction
Summary
Adult stem cells in the body are generally in a state of dormancy or the G0 phase of the cell cycle. Stem cells can be activated to re-enter the cell cycle via stimulation by specific environmental or internal factors [1,2,3]. Several theories have been proposed to explain the dormancy and activation mechanism of stem cells, including phosphorylation of RNA polymerase [13, 14], p27 gene regulation [15, 16], regulation of TGF-β/ Smad pathway [17], cell dormancy based on autophagy, biochronometer theory, and insulin/Igf pathway. It is known that 5-FU concentrates stem cells and increases the proportion of cells in the G0 phase [18, 19, 20, 21]
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