The high-throughput perturbation of long non-coding RNA reveals functional features in stem cells and across cell-types

Long non-coding RNAs (lncRNAs) were shown to regulate pluripotency and differentiation, however, a comprehensive assessment of their regulatory roles in stem cells is currently lacking. By performing a large-scale knockdown of lncRNAs (n = 390) in human induced pluripotent stem (iPS) cells, we systematically characterized their roles in self-renewal and pluripotency. Cell growth and transcriptomic assays revealed respectively, 18.3% and 29.3% of these lncRNAs in altering cellular and molecular phenotypes upon knockdown. By integrating the molecular phenotypes with chromatin-interaction assays, we identified their cis - and trans - interacting partners as potential primary targets. In addition, cell-type enrichment revealed 16 lncRNAs associated with pluripotency and we highlighted LINC02595 , CATG00000090305.1 and RP11-148B6.2 . Next, we integrated fibroblasts phenotyping data (Ramilowski et al., 2020; Genome Research) and reported that only 2.9% lncRNAs exhibited consistent cell growth phenotype, while molecular phenotype showed 66.7% agreement. This highlights their consistent primary functional roles across cell-types and the distinct secondary effects under different cellular environments. ### Competing Interest Statement The authors have declared no competing interest.