Journal
STEM CELL REPORTS
Volume 9, Issue 6, Pages 2081-2096Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2017.10.009
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Funding
- Royan Institute
- Iranian Council of Stem Cell Research and Technology
- Iran National Science Foundation (INSF)
- Iran Science Elites Federation
- National Health and Medical Research [APP1062983]
- Deutsche Forschungsgemeinschaft (ExcellenceCluster Cardiopulmonary System) [SFB TRR81 TPA02, SFB 1213 TPA02, TP B02]
- LOEWE Center for Cell and Gene Therapy
- German Center for Cardiovascular Research
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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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