| WIP1(or PPM1D), Wild-type p53-induced phosphatase1, is an oncogene, displaying high expression level in cells of multiple cancer types. Meanwhile, it is also known as a very important component in p53negative feedback pathway, hence plays a vital role in regulating homeostasis of cells. Existing studies found p53and its downstream genes played an important role in telomere-dependent aging process. However, the regulatory role of WIP1in the stem cell ageing and bone marrow failure caused by telomere dysfunction is unclear. We established of WIP1and Terc double knockout mice strain through hybridize breeding, then intercrossing to get WIP1gene deletion of GSTerc-/-mice. On this basis, Peripheral bone marrow analysis, in vivo hematopoietic reconstitution experiments, as well as other means of competitive bone marrow transplantation experiments, were used to discuss the function of WIP1and Terc double knockout HSC in adult and aging mice.The results showed that WIP1gene knockdown can extend the lifespan of G3mouse. The proportion of myeloid cells, B lymphocytes, CD4+T, CD8+T cells in bone marrow of G3WIP1-/-had no difference compare to G3mice. At the stem cell level, the number of SLAM cells increased obviously, but the number of long-term stem cells (LT), Short-term stem cells (ST) had no change in G3WIP1-/-mice. At progenitor level, the number of CMP, GMP, CLP and MEP has no difference. The result of competitive bone marrow transplantation and LSK transplantation showed that WIP1gene knockout G3mice have lower ability to reconstitute the recipient hematopoietic system. The proportion of lymphocytes in spleen of G3WIP1-/-did not increase, and myeloid invasion phenomenon had no improvement. The weight of spleen, brain, liver had no difference between G3and G3WIP1-/-mice and the weight of the kidney, heart, testicle have increased in G3WIP1-/-. Thus, WIP1gene knockdown can extend the lifespan of G3mouse but do not improve the HSC ability. |
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