show Abstracthide AbstractWe have generated induced pluripotent stem cells (iPSCs) from naked mole rat (NMR, Heterocephalus glaber) using retrovirus-mediated delivery of reprogramming factors (mouse Oct4, Sox2, Klf4 and c-Myc). NMR-iPSCs are cultured on mitomycin C-treated SNL-STO feeder cells. Although NMR-iPSCs exhibit pluripotency (the potential to differentiate into cells of the three germ layers) in vitro, they do not form teratomas in vivo. The expression of the tumour suppressor alternative reading frame (ARF) is activated in NMR-iPSCs compared with fibroblasts. NMRs have a unique frame-shift mutation in transforming-oncogene ES cell-expressed Ras (ERAS) that positively regulates tumourigenicity of mouse ESCs. To demonstrate the role of ARF activation and ERAS disruption in the tumour resistance of NMR-iPSCs, we introduced short hairpin RNA targeting ARF (shARF) and/or mouse-ERas (mERas) into NMR-iPSCs (shARF-, mERas-, or shARF/mERas-NMR-iPSCs). NMR-iPSCs acquired tumorigenicity to form teratom a by introducing shARF and mERas. Submitted overall design: The data is deep sequencing of mRNA from NMR-iPSCs (four clones: NMR-iPS 4, 10, 24 and 27), NMR skin fibroblast (two lines: H5 and H17) and NMR-iPSCs clone 24 and 27 introduced sh ARF and/or mERas (shARF-, mERas-, or shARF/mERas-NMR-iPSCs). Gene expression profiles of these cell lines were analyzed.