Abstract
Within the scope of the FANTOM6 consortium, we perform a large-scale knockdown of 200 long non-coding RNAs (lncRNAs) in human induced pluripotent stem cells (iPSCs) and systematically characterize their roles in self-renewal and pluripotency. We find 36 lncRNAs (18%) exhibiting cell growth inhibition. From the knockdown of 123 lncRNAs with transcriptome profiling, 36 lncRNAs (29.3%) show molecular phenotypes. Integrating the molecular phenotypes with chromatin-interaction assays further reveals cis- and trans-interacting partners as potential primary targets. Additionally, cell-type enrichment analysis identifies lncRNAs associated with pluripotency, while the knockdown of LINC02595, CATG00000090305.1, and RP11-148B6.2 modulates colony formation of iPSCs. We compare our results with previously published fibroblasts phenotyping data and find that 2.9% of the lncRNAs exhibit a consistent cell growth phenotype, whereas we observe 58.3% agreement in molecular phenotypes. This highlights that molecular phenotyping is more comprehensive in revealing affected pathways.
Original language | English |
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Article number | 111893 |
Journal | Cell reports |
Volume | 41 |
Issue number | 13 |
ISSN | 2211-1247 |
DOIs | |
Publication status | Published - 27 Dec 2022 |
Bibliographical note
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.Keywords
- Embryonic Stem Cells/metabolism
- Gene Expression Profiling/methods
- Humans
- Induced Pluripotent Stem Cells/metabolism
- Oligonucleotides, Antisense
- RNA, Long Noncoding/genetics
- CAGE
- CP: Stem cell research
- iPSC
- functional annotation
- gapmer ASO
- CP: Molecular biology
- long non-coding RNA