Coordination of cell differentiation and proliferation is a key issue in the development process of multi-cellular organisms and stem cells. Here we provide evidence that the establishment of adipocyte differentiation...Coordination of cell differentiation and proliferation is a key issue in the development process of multi-cellular organisms and stem cells. Here we provide evidence that the establishment of adipocyte differentiation of 3T3-L1 cells requires two processes: the licensing of an adipogenesis gene-expression program within a particular growth-arrest stage, i.e., the contact-inhibition stage, and then the execution of this program in a cell-cycle-independent manner, by which the licensed progenitors are differentiated into adipocytes in the presence of inducing factors. Our results showed that differentiation licensing of 3T3-L1 cells during the contact-inhibition stage involved epigenetic modifications such as DNA methylation and histone modifications, whereas disturbing these epigenetic modifications by DNA methylation inhibitors or RNAi during the contact-inhibition stage significantly reduced adipogenesis efficiency. More importantly, when these licensed 3T3-L1 cells were re-cultured under non-differentiating conditions or treated only with insulin, this adipogenesis commitment could be maintained from one cell generation to the next, whereby the licensed program could be activated in a cell-cycle-independent manner once these cells were subjected to adipo- genesis-inducing conditions. This result suggests that differentiation licensing and differentiation execution can be uncoupled and disparately linked to cell proliferation. Our findings deliver a new concept that cell-fate decision can be subdivided into at least two stages, licensing and execution, which might have different regulatory relationships with cell proliferation. In addition, this new concept may provide a clue for developing new strategies against obesity.展开更多
A series of silver-doped graphite-like carbon coatings was prepared on the surface of aluminum alloy using the magnetron sputtering method. The spontaneous escape behavior and inhibition mechanism of silver from graph...A series of silver-doped graphite-like carbon coatings was prepared on the surface of aluminum alloy using the magnetron sputtering method. The spontaneous escape behavior and inhibition mechanism of silver from graphite-like carbon coating were studied. The results showed that when the sample prepared with a 0.01-A current on the silver target was placed in an atmospheric environment for 0.5 h, an apparent silver escape phenomenon could be observed. However, the silver escape phenomenon was not observed for samples prepared with a 0.05-A current on the silver target if the sample was retained in a 10^(-1) Pa vacuum environment, even after 48 h. Compared with the sample placed in the atmospheric environment immediately after an ion plating process, the silver escape time lagged for 6 h. Nanometer-thick pure carbon coating coverage could effectively suppress silver escape. When the coating thickness reached700 nm, permanent retention of silver could be achieved in the silver-doped graphite-like carbon coating.As the silver residue content in the graphite-like carbon coating increased from 2.27 at.% to 5.35 at.%, the interfacial contact resistance of the coating decreased from 51mΩcm^2 to 6 mΩcm^2.展开更多
文摘Coordination of cell differentiation and proliferation is a key issue in the development process of multi-cellular organisms and stem cells. Here we provide evidence that the establishment of adipocyte differentiation of 3T3-L1 cells requires two processes: the licensing of an adipogenesis gene-expression program within a particular growth-arrest stage, i.e., the contact-inhibition stage, and then the execution of this program in a cell-cycle-independent manner, by which the licensed progenitors are differentiated into adipocytes in the presence of inducing factors. Our results showed that differentiation licensing of 3T3-L1 cells during the contact-inhibition stage involved epigenetic modifications such as DNA methylation and histone modifications, whereas disturbing these epigenetic modifications by DNA methylation inhibitors or RNAi during the contact-inhibition stage significantly reduced adipogenesis efficiency. More importantly, when these licensed 3T3-L1 cells were re-cultured under non-differentiating conditions or treated only with insulin, this adipogenesis commitment could be maintained from one cell generation to the next, whereby the licensed program could be activated in a cell-cycle-independent manner once these cells were subjected to adipo- genesis-inducing conditions. This result suggests that differentiation licensing and differentiation execution can be uncoupled and disparately linked to cell proliferation. Our findings deliver a new concept that cell-fate decision can be subdivided into at least two stages, licensing and execution, which might have different regulatory relationships with cell proliferation. In addition, this new concept may provide a clue for developing new strategies against obesity.
基金financial support of the project from the National Natural Science Foundation of China (Nos. 51571114 and 51401106)the Natural Science Foundation of Jiangsu Province (No. BK20130935)
文摘A series of silver-doped graphite-like carbon coatings was prepared on the surface of aluminum alloy using the magnetron sputtering method. The spontaneous escape behavior and inhibition mechanism of silver from graphite-like carbon coating were studied. The results showed that when the sample prepared with a 0.01-A current on the silver target was placed in an atmospheric environment for 0.5 h, an apparent silver escape phenomenon could be observed. However, the silver escape phenomenon was not observed for samples prepared with a 0.05-A current on the silver target if the sample was retained in a 10^(-1) Pa vacuum environment, even after 48 h. Compared with the sample placed in the atmospheric environment immediately after an ion plating process, the silver escape time lagged for 6 h. Nanometer-thick pure carbon coating coverage could effectively suppress silver escape. When the coating thickness reached700 nm, permanent retention of silver could be achieved in the silver-doped graphite-like carbon coating.As the silver residue content in the graphite-like carbon coating increased from 2.27 at.% to 5.35 at.%, the interfacial contact resistance of the coating decreased from 51mΩcm^2 to 6 mΩcm^2.