Although TGF-β signaling can effectively activate fibroblasts to transform to myofibroblasts, the underlying mechanisms involved in the cell fate switching for trans-differentiation have not been fully elucidated. In this study, we found the evidence of an intermediate state in the process of trans-differentiation. In the early stage of trans-differentiation, cells enter the intermediate state first with multiple characteristics such as accelerating cell cycle, metabolic switching, enhanced anti-apoptotic ability, and pluripotency, which is very similar to the early stage of reprogramming. As the trans-differentiation continues, these characteristics get switched. Therefore, trans-differentiation appears to require the switching of cell proliferation ability, metabolic pathway, and “stemness” to complete the process. In this study, we can conclude that an intermediate state may be necessary with high pluripotency in trans-differentiation from fibroblasts to myofibroblasts. Only after passing the intermediate state, the trans-differentiation is finally completed and will not easily return to the original state.

尽管 TGF-β 信号传导可以有效激活成纤维细胞转化为肌成纤维细胞，但转分化的细胞命运转换的潜在机制尚未完全阐明。在这项研究中，我们发现了转分化过程中存在中间状态的证据。在转分化早期，细胞首先进入中间状态，具有加速细胞周期、代谢转换、抗凋亡能力增强、多能性等多重特征，这与重编程的早期非常相似。随着转分化的继续，这些特征会发生变化。因此，转分化似乎需要细胞增殖能力、代谢途径和“干性”的转换才能完成这一过程。在这项研究中，我们可以得出结论，在从成纤维细胞到肌成纤维细胞的转分化过程中，具有高多能性的中间状态可能是必要的。只有过了中间状态，转分化才最终完成，不会轻易回到原来的状态。