Mesenchymal stem cells (MSCs) are multipotent adult stem cells that can self-renew and differentiate into a variety of cell types including chondrocytes, osteocytes and adipocytes. MSCs reside in bone marrow, adipose tissues, cord blood, peripheral blood, placenta, Wharton’s jelly, fetal liver and lung among others. MSCs represent one of the most promising stem cells for regenerative medicine due to their multipotency, immunoprivileged properties and easy expansion in vitro. So far, MSCs are already in various phases of clinical application [1-4]. Their most immediate use is in the orthopedic context due to the clear demonstration of their ability to differentiate into bone and cartilage [5-8]. It has been 5 decades since Friedenstein et al described clonal and plastic adherent stromal cells from bone marrow in the 1960s [9,10]. Although there are a handful of genes suggesting possible MSC stemness markers, the molecular basis underlying MSC stemness, especially the key transcription factor to MSC stemness, is still poorly understood.