Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State Pluripotency
Author(s) -
Sharif Moradi,
Ali SharifiZarchi,
Amirhossein Ahmadi,
Sepideh Mollamohammadi,
Alexander Stubenvoll,
Stefan Günther,
Ghasem Hosseini Salekdeh,
Sassan Asgari,
Thomas Braun,
Hossein Baharvand
Publication year - 2017
Publication title -
stem cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.207
H-Index - 76
ISSN - 2213-6711
DOI - 10.1016/j.stemcr.2017.10.009
Subject(s) - biology , embryonic stem cell , microrna , psychological repression , microbiology and biotechnology , genetics , rex1 , gene , gene expression , induced pluripotent stem cell
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.
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