Small RNA sequencing reveals Dlk1-Dio3 locus-embedded microRNAs as major drivers of ground-state pluripotency

Sharif Moradi, Ali Sharifi-Zarchi, Amirhossein Ahmadi, Sepideh Mollamohammadi, Alexander Stubenvoll, Stefan Günther, Ghasem Hosseini Salekdeh, Sassan Asgari, Thomas Braun*, Hossein Baharvand

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Pages (from-to)2081-2096
Number of pages16
JournalStem Cell Reports
Volume9
Issue number6
DOIs
Publication statusPublished - 12 Dec 2017
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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