The study investigates the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs) during the derivation of human induced pluripotent stem cells (iPSCs) and identifies lincRNAs linked to pluripotency. Among these, 10 lincRNAs were found to be elevated in iPSCs compared to embryonic stem cells (ESCs), suggesting their potential role in promoting iPSC emergence. Using loss- and gain-of-function approaches, the researchers found that one such lincRNA, lincRNA-RoR (ST8SIA3), modulates reprogramming, providing the first demonstration of critical functions of lincRNAs in the derivation of pluripotent stem cells. The study also reveals that lincRNA-ST8SIA3 is directly regulated by pluripotency transcription factors and plays a role in promoting survival in iPSCs and ESCs by preventing the activation of cellular stress pathways, including the p53 response.The study investigates the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs) during the derivation of human induced pluripotent stem cells (iPSCs) and identifies lincRNAs linked to pluripotency. Among these, 10 lincRNAs were found to be elevated in iPSCs compared to embryonic stem cells (ESCs), suggesting their potential role in promoting iPSC emergence. Using loss- and gain-of-function approaches, the researchers found that one such lincRNA, lincRNA-RoR (ST8SIA3), modulates reprogramming, providing the first demonstration of critical functions of lincRNAs in the derivation of pluripotent stem cells. The study also reveals that lincRNA-ST8SIA3 is directly regulated by pluripotency transcription factors and plays a role in promoting survival in iPSCs and ESCs by preventing the activation of cellular stress pathways, including the p53 response.