Regulation of Nodal-Lefty Expression by TGF-^|^beta; Induced Pluripotent Stem (iPS) Cells Derived from Mouse Oral Mucosal Tissue

Abstract

Nodal-Lefty signaling is essential for embryonic stem cell pluripotency and growth control of ES cells, which play an important role in tumorigenic phenotype. We recently reported that TGF-increases Lefty expression in pancreatic cancer cells. However, a previous study has shown that TGF-is unable to induce Nodal and Lefty expression in ES or induced pluripotent stem (iPS) cells. We established an iPS cell line from mouse oral tissue via retroviral gene transfer of OCT3/4, Sox2, c-Myc and KLF4. The obtained iPS cells expressed undifferentiated markers, such as OCT4, Nanog and SSEA1. We observed induction of the Lefty gene in these iPS cells, as well as in mouse ES cells in ES medium either with or without TGF-treatment. This is the first report showing Lefty expression in iPS cells. We then investigated the signaling relationship between TGF-and mitogen-activated protein kinase (MAPK) by using specific kinase inhibitors, and found that p38 has some effect on Lefty expression. Taken together, these results suggest that iPS cells from oral tissue possess a different mechanism for Lefty expression than mouse ES cells. TGF-with p38 is able to regulate Lefty expression in iPS cells.