P.137ETS1 facilitates muscle satellite cell proliferation and stemness perpetuation

Abstract

Muscle stem cells (MuSCs) possess remarkable regenerative capacity which is controlled by various molecules. Understanding these regulatory pathways is a promising therapeutic approach to many muscle diseases. Here, we reported ETS1 as an important transcription factor which regulates MuSCs proliferation and stemness perpetuation. ETS1 is known to associate in various biological processes, especially in immune system. Aberrant expression of ETS1 has been described in many types of cancer. However, its function in musculoskeletal system remains unclear. Using transcriptomic analysis, we identified ETS1 which is highly expressed in proliferating MuSCs compared to differentiating cells. qRT-PCR showed significant reduction of ETS1 expression during the course of differentiation which was confirmed by immunostaining and western blot. We constructed ETS1-retroviral vector and performed forced overexpression of ETS1. Despite being cultured in differentiation media, ETS1-overexpressing MuSCs could maintain Pax7 expression and proliferation potential. In addition, most of the cells remained unfused and myotube formation was obviously scarce. On the contrary, with RNA interference, we observed decreased EdU and KI67 incorporation in ETS1 knocked-down MuSCs. Taken together, our findings suggest that ETS1 is one of the essential regulators of MuSCs proliferation and stem cell property. Functionally knockdown of ETS1 significantly affects proliferation of MuSCs.