The Regulation Of Reactive Oxygen Species In Intestinal Stem Cells

Stem cells are a class of the original unspecialized cells, which have the capacity of self-renew and can differentiate into specific tissue cells. As the primary basis for regenerative medicine research, the clinical applications stem cell therapy is an important goal of modern biomedical. However, how to control the survival and differentiation of stem cells is a huge challenge in a complex organism environment. As we know, operating the internal and external environment of stem cells could make a change of their self-renew and differentiation. However, there is not a scientific standard to guide the application of stem cells in clinical treatment. And reactive oxygen species (ROS) is an important molecule in the regulation of cell environment. Our study established a correspondence between ROS and stem cells under different pathological conditions. And explore how to manipulate intracellular ROS levels to regulate stem cell state.Drosophila as a model organism, we use Drosophila intestinal epithelial system as the research object. Three kinds of pathological model were established as follows. Firstly, be extracellular matrix adhesion defects which may cause cell loss. Secondly, stem cell excessive proliferation model, which may result in a tumor-like population. Thirdly, be divorced from the matrix of tumor-like stem cells model. Semi-quantitative detection of intracellular ROS levels at different pathological conditions. Then take advantage of Drosophila genetics, by changing the expression of genes related to control the ROS levels in vivo environment, thereby regulating the physiological state of stem cells to promote stem cell achieved rescue from the pathological state.We found that low levels of ROS contribute to rescue stem cells loss from the matrix, and to suppress the development of tumors, but induce tumor-like cells to develop into tumors. Higher levels of ROS will strengthen stem cells loss from the matrix, and will increase the ability of stem cells develop into tumor cells, but induce the tumor-like cells with extracellular matrix adhesion defects to apoptosis. While extremely high levels of ROS contribute to rescue the stem cells with extracellular matrix adhesion defects loss from the matrix, and induce tumor-like cells step into apoptosis, and contribute to the tumor-like cells with extracellular matrix adhesion defects remain survive, in addition to inhibit the formation of tumor. It means that, ROS levels of stem cells with the pathological state does exist a certain relationship. However, this correspondence is not a simply positive or negative correlation, but it depends on a dose effect.Our research on the effects of different levels of ROS on stem cell survival, proliferation and tumor cell transformation to deepen the understanding of the regulation of stem cells, and provides a theoretical basis to resolve the problem of low survival rates and easy carcinogenesis in clinical stem cell therapy as well as antioxidants in cancer therapy.