The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification.

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Boroviak, Thorsten 
Loos, Remco 

The precise relationship of embryonic stem cells (ESCs) to cells in the mouse embryo remains controversial. We present transcriptional and functional data to identify the embryonic counterpart of ESCs. Marker profiling shows that ESCs are distinct from early inner cell mass (ICM) and closely resemble pre-implantation epiblast. A characteristic feature of mouse ESCs is propagation without ERK signalling. Single-cell culture reveals that cell-autonomous capacity to thrive when the ERK pathway is inhibited arises late during blastocyst development and is lost after implantation. The frequency of deriving clonal ESC lines suggests that all E4.5 epiblast cells can become ESCs. We further show that ICM cells from early blastocysts can progress to ERK independence if provided with a specific laminin substrate. These findings suggest that formation of the epiblast coincides with competence for ERK-independent self-renewal in vitro and consequent propagation as ESC lines.

Animals, Biomarkers, Blastocyst Inner Cell Mass, Cell Differentiation, Cell Line, Cell Lineage, Cell Proliferation, Clone Cells, Embryo Culture Techniques, Embryo Implantation, Embryonic Stem Cells, Extracellular Signal-Regulated MAP Kinases, Gene Expression Profiling, Gene Expression Regulation, Developmental, Germ Layers, Gestational Age, Laminin, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Inbred CBA, Phenotype, Pluripotent Stem Cells, Transcription Factors
Journal Title
Nat Cell Biol
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Springer Science and Business Media LLC
Biotechnology and Biological Sciences Research Council (BB/G015678/1)
Medical Research Council (G1001028)
MRC (G1100526)
Medical Research Council (MC_PC_12009)
Wellcome Trust (091484/Z/10/Z)