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Small RNA sequencing reveals dlk1-dio3 locus-embedded microRNAs as major drivers of ground-state pluripotency

Moradi, S ; Sharif University of Technology

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  1. Type of Document: Article
  2. DOI: 10.1016/j.stemcr.2017.10.009
  3. Abstract:
  4. Ground-state pluripotency is a cell state in which pluripotency is established and maintained through efficient repression of endogenous differentiation pathways. Self-renewal and pluripotency of embryonic stem cells (ESCs) are influenced by ESC-associated microRNAs (miRNAs). Here, we provide a comprehensive assessment of the “miRNome” of ESCs cultured under conditions favoring ground-state pluripotency. We found that ground-state ESCs express a distinct set of miRNAs compared with ESCs grown in serum. Interestingly, most “ground-state miRNAs” are encoded by an imprinted region on chromosome 12 within the Dlk1-Dio3 locus. Functional analysis revealed that ground-state miRNAs embedded in the Dlk1-Dio3 locus (miR-541-5p, miR-410-3p, and miR-381-3p) promoted pluripotency via inhibition of multi-lineage differentiation and stimulation of self-renewal. Overall, our results demonstrate that ground-state pluripotency is associated with a unique miRNA signature, which supports ground-state self-renewal by suppressing differentiation. Ground-state pluripotency is a cell state in which pluripotency is maintained through inhibition of differentiation. In this paper, Baharvand and colleagues report that ground-state pluripotency is associated with a unique microRNA signature. They find that ground-state microRNAs, which are mostly encoded by the Dlk1-Dio3 locus, contribute to the maintenance of ESCs through stimulating self-renewal and inhibiting differentiation. © 2017 The Authors
  5. Keywords:
  6. Differentiation ; Dlk1-Dio3 locus ; Ground-state pluripotency ; Self-renewal ; Sfmbt2 locus ; Small RNA sequencing ; Dio3 protein ; Dlk1 protein ; MicroRNA ; MicroRNA 106a 363 ; MicroRNA 106b 25 ; MicroRNA 10a 5p ; MicroRNA 127 3p ; MicroRNA 142a 5p ; MicroRNA 16 5p ; MicroRNA 17 92 ; MicroRNA 182 ; MicroRNA 182 5p ; MicroRNA 183 ; MicroRNA 183 5p ; MicroRNA 203 3p ; MicroRNA 211 5p ; MicroRNA 21a 5p ; MicroRNA 290 ; MicroRNA 295 ; MicroRNA 302 367 ; MicroRNA 302b ; MicroRNA 381 3p ; MicroRNA 410 3p ; MicroRNA 467c 5p ; MicroRNA 541 5p ; MicroRNA let 7a 5p ; MicroRNA let 7g 5p ; Piwi interacting RNA ; Protein ; Unclassified drug ; Cell differentiation ; Cell growth ; Cell lineage ; Chromosome ; Chromosome 12 ; Comparative study ; Controlled study ; Embryo ; Gene expression ; Gene locus ; Genome imprinting ; Human ; Human cell ; Human embryonic stem cell ; Nucleotide sequence ; Pluripotent stem cell ; Priority journal ; RNA sequence ; Stem cell culture ; Stem cell self-renewal ; Upregulation
  7. Source: Stem Cell Reports ; Volume 9, Issue 6 , 2017 , Pages 2081-2096 ; 22136711 (ISSN)
  8. URL: https://www.sciencedirect.com/science/article/pii/S2213671117304642