Glis family proteins are differentially implicated in the cellular reprogramming of human somatic cells

// Seo-Young Lee 1, * , Hye Bin Noh 1, * , Hyeong-Taek Kim 1 , Kang-In Lee 1 and Dong-Youn Hwang 1 1 Department of Biomedical Science, College of Life Science, CHA University, Seongnamsi, Gyeonggido 13488, Korea * These authors have contributed equally to this work Correspondence to: Dong-Youn Hwang, email: hdy@cha.ac.kr Keywords: somatic cells, induced pluripotent stem cells, glis family proteins, cellular reprogramming, adipose derived stromal cells Received: May 10, 2017 Accepted: June 19, 2017 Published: August 18, 2017 ABSTRACT The ground-breaking discovery of the reprogramming of somatic cells into pluripotent cells, termed induced pluripotent stem cells (iPSCs), was accomplished by delivering 4 transcription factors, Oct4, Sox2, Klf4, and c-Myc, into fibroblasts. Since then, several efforts have attempted to unveil other factors that are directly implicated in or might enhance reprogramming. Importantly, a number of transcription factors are reported to retain reprogramming activity. A previous study suggested Gli-similar 1 (Glis1) as a factor that enhances the reprogramming of fibroblasts during iPSC generation. However, the implication of other Glis members, including Glis2 and Glis3 (variants 1 and 2), in cellular reprogramming remains unknown. In this study, we investigated the potential involvement of human Glis family proteins, including hGlis1-3, in cellular reprogramming. Our results demonstrate that hGlis1, which is reported to reprogram human fibroblasts, promotes the reprogramming of human adipose-derived stromal cells (hADSCs), indicating that the reprogramming activity of Glis1 is not cell type-specific. Strikingly, hGlis3 promoted the reprogramming of hADSCs as efficiently as hGlis1. On the contrary, hGlis2 showed a strong negative effect on reprogramming. Together, our results reveal clear differences in the cellular reprogramming activity among Glis family members and provide valuable insight into the development of a new reprogramming strategy using Glis family proteins.