An intermediate state in trans-differentiation with proliferation, metabolic, and epigenetic switching

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.