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

Chi Wai Yip, Chung-Chau Hon, Kayoko Yasuzawa, Divya Mundackal Sivaraman, Jordan A. Ramilowski, Youtaro Shibayama, Saumya Agrawal, Anika V. Prabhu, Callum Parr, Jessica Severin, Yan Jun Lan, Josee Dostie (+19 others)
2022 bioRxiv   pre-print
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
more » ... henotypes 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.
doi:10.1101/2022.02.16.480297 fatcat:adnyvqfvgnbtnlkg2xmiiovxz4