Different Types Of Adult Stem Cells To Dna Damage Responses

People all over the world is living longer than ever before and it is a serious society problem.This global aging urges a better understanding of the molecular basis underlying aging and age-associated diseases. Telomere shorting was considered as one of the aging mechanisms. The telomere dysfunctional mouse provides an invaluable model for studies on telomere-driven aging in stem cell compartment in vivo. G3Terc-/-mouse exhibit the shorten telomere length as a result of the loss of telomerase, and further activated the DNA damage pathway, which induce cell-intrinsic mechanisms and environmental alterations.Exonucleasel (Exol) is one of mismatch repair related genes that involved in telomere dysfunction induced DNA damage pathway. Deletion of Exol can prevent the DNA damage pathway in small intestine crypt stem cell and further ameliorated the atrophy small intestine. However, the (?) of Exol on G3Terc-/-mouse different tissue stem cell is unknown.In our study, Exol knockout cannot rescue the self-renewal of G3Terc-/-mouse's hematopoietic stem cell. Compared with wild type mouse, the percentage of donor derived cell in G3Terc-/-mouse decreased significantly. We further studied the neural stem cell and mesenchymal stem cell, and observed that Exol knockout didn't rescue the self-renewal of G3Terc-/-mouse's neural stem cell and mesenchymal stem cell, and the NSC and MSC's DNA damage pathway cannot be prevented. Overall, our study first verified that, different tissue stem cells respond to same checkpoint may act distinct. It provides the new proof to study the impact of many other genes in different type of tissue stem cell, and also provides inspiration for the study of stem cell aging and regenerative medicine.Telomere dysfunction contributes to cell-extrinsic alterations that impair stem cell function of differentiation. It can also provoke the defects of hematopoietic environment that impair B lymphopoiesis but increase myeloid proliferation in aging G3Terc-/-mice. And the impairment in B and T lymphopoiesis in aging telomere-dysfunctional mice was mainly due to alterations of the systemic environment. But it is unknown whether serum can impair the repopulation capacity of HSC directly. The impaired system environment of G3Terc-/-mouse responsible for the reduced ability of HSC repopulation capacity rather than the HSC stromal niche. There is a loss of HSC cells quiescence maintain in cultures supplemented with G3Terc-/-serum. The high expression level of p21and TGF-β maybe partially responsible for the impaired HSC function when exposed to G3Terc-/-serum. Here, we first show that G3Terc-/-serum can impair the repopulation capacity of HSC directly.Overall, our study first verified that different tissue stem cells respond to same checkpoint may act distinct. And also first show that, it is the impaired system environment of G3Terc-/-mouse responsible for the reduced ability of HSC repopulation. It provides new ideas and strategies for study of regulatory mechanisms of stem cell damage.