Year: 2012
Type: article
Abstract: Mouse embryonic stem (ES) cells grown in serum exhibit greater heterogeneity in morphology and expression of pluripotency factors than ES cells cultured in defined medium with inhibitors of two kinases (Mek and GSK3), a condition known as "2i" postulated to establish a naive ground state. We show that the transcriptome and epigenome profiles of serum- and 2i-grown ES cells are distinct. 2i-treated cells exhibit lower expression of lineage-affiliated genes, reduced prevalence at promoters of the repressive histone modification H3K27me3, and fewer bivalent domains, which are thought to mark genes poised for either up- or downregulation. Nonetheless, serum- and 2i-grown ES cells have similar differentiation potential. Precocious transcription of developmental genes in 2i is restrained by RNA polymerase II promoter-proximal pausing. These findings suggest that transcriptional potentiation and a permissive chromatin context characterize the ground state and that exit from it may not require a metastable intermediate or multilineage priming.
Source: Cell
Authors: Hendrik Marks, Tüzer Kalkan, Roberta Menafra, Sergey Denissov, Kenneth Jones, Helmut Hofemeister, Jennifer Nichols, Andrea Kranz, A. Francis Stewart, Austin Smith, Hendrik G. Stunnenberg
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,400
Awards: G2304404308, Wellcome Trust MRC Cambridge Stem Cell Institute, WELLCOME TRUST CENTRE FOR STEM CELL RESEARCH, European Consortium for Systematic Stem Cell Biology, Development of Laser-Based Technologies and Prototype Instruments for Genome-Wide Chromatin ImmunoPrecipitation Analyses, Systems biology approaches to understand cell pluripotency Acronym: PluriSys
OpenAlex ID: W2163679188