The Two Organizations Based On A Mouse Model Of Stem Cell Research

Endogenous Lung Stem Cells are the lung cells that have the capability of self-renewal and capable of regeneration of specific cell lineages in the lung under certain conditions. Endogenous lung stem cells maintain pulmonary homeostasis, and also play an important role in the repair of lung after injury. Aging may change the capability of lung stem cell regeneration and differentiation, and could therefore influence lung function and contribute to pulmonary diseases. The incidence of pulmonary fibrosis increases with age, independent of exposure to common environmental risk factors. Myofibroblasts is closely related to the occurrence of pulmonary fibrosis. We analyzed the proportion of lung stem cells of different lung injury mouse models induced by different methods, and evaluate the influence of aging in these processes. We also compared two methods for isolating lung stem cell:CD31-CD45-Sca-1+CD34+and CD31-CD45-Sca-l-EpCAM+. Our result shows that the CD31-CD45-Sca-1-EpCAM+is more suitable for distinguish distal lung epithelial stem cells and mesenchymal stem cells. By establish of lung injury mouse model we studied the influence of aging on the lung injury and repair, and examine the function of lung stem cells during repair of lung injury. The results suggested that aging didn't change the proportion of lung stem cells (including the distal lung epithelial stem cells and lung mesenchymal stem cells/progenitor cells) under normal physiological conditions. However, during the repair process of lung injury, lung epithelial stem cells and lung mesenchymal stem cells/progenitor cells decreased. The myofibroblasts ratio of mice in different age were analyzed. The data suggested that aging led to altered composition of lung mesenchymal stem cells, which showed an increased proportion of myofibroblast. Our data suggest that lung stem cell aging might contribute to the pathogenesis of pulmonary fibrosis. RunX3 (Runt-related transcription factor 3) is related to cell proliferation, apoptosis, differentiation, and also have effects on immune system and carcinogenesis. To study the role of RunX3 gene in hematopoietic stem cells (HSCs) self-renewal and differentiation, number and function of HSC in RunX3 knockout mouse were determined by flow cytometry and competitive bone marrow transplantation experiment.Competitive bone marrow transplantation is the standard method to determine the self-renewal capacity of the stem cell. At 3 months after transplantation, recipient mice were treated with 5-FU, to further evaluate the long-term self-renewal and differentiation capacity of HSCs of the RunX3 knockout mice. The frequency of RunX3-/- HSCs derived myeloid cells in total myeloid cells was much higher than those of wildtype HSCs derived cells. Recipient mice were then treated with 5-FU. After one week, the frequency of RunX3-/- HSCs derived myeloid cells was much higher than those of wildtype HSCs derived cells. A decrease of RunX3-/- HSCs derived B cells in the peripheral blood was only observed at one month after 5-FU treatment.These data show that the number of HSCs in RunX3 knockout mouse was same as those of wildtype control mice. In normal condition, RunX3 gene shows no affect on HSC homeostasis. In the setting of competitive transplantation, RunX3 gene is not essential in HSC self-renewal, but appear to promote the HSC differentiate toward myeloid lineage. Followed by myeloablation, RunX3 deletion may further increase the skewed differention potential of transplanted HSCs, which is increased differentiate to myeloid lineage but decreased differentiate to B lymphocytes.