A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation
Year: 2017
Type: article
Abstract: Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) linc1281, hereafter Ephemeron (Eprn), that modulates the dynamics of exit from naïve pluripotency. Eprn deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of Eprn, Lin28a expression is reduced which results in persistence of let-7 microRNAs, and the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. Dnmt3a/b deletion retards ES cell transition, correlating with delayed Nanog promoter methylation and phenocopying loss of Eprn or Lin28a. The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of naïve pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. Eprn illustrates how lncRNAs may introduce species-specific network modulations.
Source: eLife
DOI: 10.7554/elife.23468
Institutions: Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, University of California, Berkeley, The Gurdon Institute, Cold Spring Harbor Laboratory, Wellcome Trust, University of Portsmouth, Babraham Institute, Wellcome Sanger Institute, Integrated DNA Technologies (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: American Cancer Society, California Institute for Regenerative Medicine, Tobacco-Related Disease Research Program, California Institute of Regenerative Medicine, Wellcome Trust, Cancer Research UK, Royal Society, European Commission, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council, European Research Council, National Cancer Institute, National Institute of General Medical Sciences
Awards: Interrogating the roles of miRNAs in entering and exiting ground state pluripotency in embryonic stem cells., G2537149883, The Road from Pluripotency to Lineage Determination., Core support for the Wellcome Trust Cancer Research UK Gurdon Institute., G3725617714, G3773452209, G3985125482, G4384873914, G4416467271, European Consortium for Systematic Stem Cell Biology, G4732027917, G4777905834, G4892066809, G490104470, The Road from Pluripotency to Lineage Determination., G5164774769, G5570099221, G5605280477, G5753100354, G5947339487, G660280834, G666505512, G6669327581, Interrogating the roles of miRNAs in entering and exiting ground state pluripotency in embryonic stem cells., G7280018357, G7505324234, G7579029867, Stem Cell Derivation, Differentiation and Transplantation, G789504050, Core support for the Wellcome Trust Cancer Research UK Gurdon Institute., G8416054600, Comparative transcriptional control of establishment, maintenance and collapse of naive pluripotency in rodents and primates in vivo, G8961340570
OpenAlex ID: W2743376548