Klf2 contributes to the stemness and self-renewal of human bone marrow stromal cells

Mesenchymal stem cells (MSCs) have shown great therapeutic potential in clinical trials; however, loss of pluripotency due to culture senescence is a major factor limiting their application. Understanding the physiology of stem cell self-renewal and stemness, and identifying the molecules that regulate these processes, are critical to future advances in tissue and organ regeneration. The Kruppel-like factor (Klf) family are key transcription factors implicated in self-renewal of embryonic stem cells. Here we identify Klf2 as a crucial transcription factor in undifferentiated human bone marrow stromal cells (hBMSCs), as indicated by gene expression in three culture media. To investigate the role of Klf2 in detail, an overexpression study using a lentiviral system in hBMSCs was performed. After Klf2 overexpression, cell proliferation was increased. The expression of pluripotency-associated genes, including Oct4, Nanog, and Rex1, was also upregulated by Klf2 overexpression. In addition, quantitative RT-PCR indicated a lower level of expression of differentiation related genes in Klf2 overexpressing cells as compared to control cells. Our results identify a functionally conserved role for Klf2 in hBMSCs, in which its expression is biologically important for stemness and self-renewal. These results are the first to show a role for Klf2 in the proliferation and pluripotency of hBMSCs.