Adipogenesis licensing and execution are disparately linked to cell proliferation

房间区别和增长的协作是在多细胞的有机体和干细胞的发展过程的一个关键问题。这里，我们提供 3T3-L1 房间的 adipocyte 区别的建立要求二个过程的证据：在一个特别生长拘捕阶段以内准许一个 adipogenesis 基因表示程序，即，以一种 cell-cycle-independent 方式，准许的祖先被面对导致因素区分进 adipocytes 的这个程序的接触抑制阶段，然后执行。我们的结果证明在接触抑制阶段期间 3T3-L1 房间准许的区别包含了象 DNA methylation 那样的 epigenetic 修正和 histone 修正，而显著地在接触抑制阶段期间由 DNA methylation 禁止者或 RNAi 扰乱这些 epigenetic 修正减少的 adipogenesis 效率。更重要地，当这些准许的 3T3-L1 房间在非区分的条件下面是 re 有教养的或仅仅与胰岛素对待时，这 adipogenesis 承诺能从一房间代被维持到下一个，一旦这些房间受到导致 adipogenesis，准许的节目由此能以一种 cell-cycle-independent 方式被激活，调节。这结果建议准许的区别和区别执行能被解开并且迥异地连接了到房间增长。我们的调查结果陈述房间命运决定能被细分进至少二个阶段的一个新概念，准许并且执行，它可能与房间增长有不同规章的关系。另外，这个新概念可以为对肥胖开发新策略提供线索。

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.