Antisense-oligonucleotide-mediated perturbation of long non-coding RNA reveals functional features in stem cells and across cell types

• DOI: 10.1016/j.celrep.2022.111893
• Publication Date: 2022-12-27T15:38:17Z
• Authors: Chi Wai Yip; Chung-Chau Hon; Kayoko Yasuzawa; Divya M. Sivaraman; Jordan A. Ramilowski; Youtaro Shibayama; Saumya Agrawal; Anika V. Prabhu; Callum Parr; Jessica Severin; Yan Jun Lan; Josée Dostie; Andreas Petri; Hiromi Nishiyori-...; Michihira Tagami; Masayoshi Itoh; Fernando López-Re...; Tsukasa Kouno; Jen-Chien Chang; Joachim Luginbühl; Masaki Kato; Mitsuyoshi Murata; Wing Hin Yip; Xufeng Shu; Imad Abugessaisa; Akira Hasegawa; Harukazu Suzuki; Sakari Kauppinen; Ken Yagi; Yasushi Okazaki; Takeya Kasukawa; Michiel de Hoon; Piero Carninci; Jay W. Shin
• Keywords: 0301 basic medicine; iPSC; long non-coding RNA; Gene Expression Profiling; Induced Pluripotent Stem Cells; Embryonic Stem Cells/metabolism; functional annotation; Oligonucleotides, Antisense; 3. Good health; Induced Pluripotent Stem Cells/metabolism; 03 medical and health sciences; CP: Stem cell research; CAGE; Humans; CP: Molecular biology; RNA, Long Noncoding; gapmer ASO; Gene Expression Profiling/methods; RNA, Long Noncoding/genetics; Embryonic Stem Cells

Within the scope of FANTOM6 consortium, we perform a large-scale knockdown 200 long non-coding RNAs (lncRNAs) in human induced pluripotent stem cells (iPSCs) and systematically characterize their roles self-renewal pluripotency. We find 36 lncRNAs (18%) exhibiting cell growth inhibition. From 123 with transcriptome profiling, (29.3%) show molecular phenotypes. Integrating phenotypes chromatin-interaction assays further reveals cis- trans-interacting partners as potential primary targets. Additionally, cell-type enrichment analysis identifies associated pluripotency, while LINC02595, CATG00000090305.1, RP11-148B6.2 modulates colony formation iPSCs. compare our results previously published fibroblasts phenotyping data that 2.9% exhibit consistent phenotype, whereas observe 58.3% agreement This highlights is more comprehensive revealing affected pathways.