Nanog is a transcription factor identified by its ability to maintain the self-renewal of ES cells in the absence of leukemia inhibitory factor (LIF). Nanog protein contains an N-terminal domain (ND), a DNA-binding homeobox domain (HD) and a C-terminal domain (CD). We previously reported that the CD in Nanog is a transcriptional activation domain essential for the in vivo function of Nanog. Here we demonstrated that the ND in Nanog is also functionally important. Deletion of the ND reduces the transcriptional activity of Nanog on either artificial reporters or native Nanog promoters. This truncated Nanog is also less effective in regulating the endogenous Nanog target genes. Furthermore, the ND truncation disrupted the ability of Nanog to maintain ES cell self-renewal as well. We found that the ND is not required for the nuclear localization of Nanog. These results suggest that the regulation of endogenous pluripotent genes such as oct3/4 and rex-1 is required for the in vivo function of Nanog.
In 2006,an article published in Cell by Shinya Yamanaka took by surprise the stem cell research community. By performing systematic retroviral transduction of factors enriched in embryonic stem (ES) cells,the authors demonstrated the reprogramming of mouse fibroblasts into an ES cell-like state. These cells,baptized iPS (induced pluripotent stem) cells,were immediately recognized as a ground-breaking discovery. Subsequently,the same authors and other groups reported a similar achievement with human fibroblasts. Two years later,the number of top quality papers on iPS is astonishing,and interest in the scientific community has risen to a fever pitch. But although iPS has the potential to revolutionize Regenerative Medicine,important questions still remain unanswered. Work from multiple laboratories worldwide including ours is focused on deciphering the molecular mechanisms of iPS,and trying to improve the technique to make it suitable for the clinic. In this review article we briefly discuss the past,present and future of iPS,with emphasis on urgent issues to be solved.
