Human iPS cells provide a new platform to investigate disease etiology and devise novel therapies in Regenerative Medicine. The objective of our proposed research is to gain a deep understanding of the molecular mechanisms that underlie reprogramming of human somatic cells to the iPS cell state. Our proposal is based on a genome-wide functional screen in the process of human iPS cell generation that was recently carried out in our lab. This has been a rich source of data that we have mined in several different and very insightful ways. The specific goals of this research were to identify novel pathways that act as barriers to human iPS cell generation, and to dissect the mechanism of action of one of those barriers. Both goals were achieved and surpassed, and therefore this research can be considered successfully completed. The results uncover novel barriers to reprogramming and the complex ways by which they cooperate to oppose dedifferentiation, with important implications both for Regenerative Medicine and Cancer Research. Our findings also shed light on alternative states of human pluripotency.
Our progress to date includes two publications reporting part of our findings:
1. Qin et al., “Systematic identification of barriers to human iPSC generation.” Cell 158:449 (2014).
2. Diaz et al., “HiTSelect: a comprehensive tool for high-complexity-pooled screen analysis.” Nucleic Acid Research 43(3):e16 (2015)
A 3rd publication arising from this research is currently under review.