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Time-resolved small-RNA sequencing identifies micrornas critical for formation of embryonic stem cells from the inner cell mass of mouse embryos

Moradi, S ; Sharif University of Technology | 2023

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  1. Type of Document: Article
  2. DOI: 10.1007/s12015-023-10582-6
  3. Publisher: Springer , 2023
  4. Abstract:
  5. Abstract: Cells of the inner cell mass (ICM) acquire a unique ability for unlimited self-renewal during transition into embryonic stem cells (ESCs) in vitro, while preserving their natural multi-lineage differentiation potential. Several different pathways have been identified to play roles in ESC formation but the function of non-coding RNAs in this process is poorly understood. Here, we describe several microRNAs (miRNAs) that are crucial for efficient generation of mouse ESCs from ICMs. Using small-RNA sequencing, we characterize dynamic changes in miRNA expression profiles during outgrowth of ICMs in a high-resolution, time-course dependent manner. We report several waves of miRNA transcription during ESC formation, to which miRNAs from the imprinted Dlk1-Dio3 locus contribute extensively. In silico analyses followed by functional investigations reveal that Dlk1-Dio3 locus-embedded miRNAs (miR-541-5p, miR-410-3p, and miR-381-3p), miR-183-5p, and miR-302b-3p promote, while miR-212-5p and let-7d-3p inhibit ESC formation. Collectively, these findings offer new mechanistic insights into the role of miRNAs during ESC derivation. Graphical Abstract: [Figure not available: see fulltext.] © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature
  6. Keywords:
  7. Blastocyst ; Differentiation ; ESC derivation ; Ground-state pluripotency ; MicroRNA profiling ; Non-coding RNA ; Pluripotency ; Stemness
  8. Source: Stem Cell Reviews and Reports ; Volume 19, Issue 7 , 2023 , Pages 2361-2377 ; 26293269 (ISSN)
  9. URL: https://link.springer.com/article/10.1007/s12015-023-10582-6