Qin, H. et al. Cell 158, 449–461 (2014).

The ability to reprogram somatic cells to induced pluripotency has revolutionized many areas of biological research. For the most part, however, this process is quite inefficient. In recent work, Qin et al. carried out pooled short hairpin RNA (shRNA) screens to systematically identify genes that function as barriers to reprogramming. They screened almost 20,000 human genes with 30 shRNAs per gene in human BJ fibroblasts undergoing reprogramming with lentivirally delivered factors. Using sequencing, they identified genes that are more likely to be knocked down in cells expressing the pluripotency marker TRA-1-81. Statistical analysis and further validation led to the identification of 956 genes as barriers to reprogramming, including genes involved in processes such as cell adhesion, endocytosis and ubiquitination. The researchers make their data available as an online resource.