The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification.
Nature cell biology
MetadataShow full item record
Boroviak, T., Loos, R., Bertone, P., Smith, A., & Nichols, J. (2014). The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification.. Nature cell biology, 16 (6), 516-528. https://doi.org/10.1038/ncb2965
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.
Cell Line, Clone Cells, Pluripotent Stem Cells, Germ Layers, Animals, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Extracellular Signal-Regulated MAP Kinases, Laminin, Transcription Factors, Embryo Culture Techniques, Gene Expression Profiling, Cell Differentiation, Cell Proliferation, Gene Expression Regulation, Developmental, Cell Lineage, Gestational Age, Embryo Implantation, Phenotype, Embryonic Stem Cells, Blastocyst Inner Cell Mass, Mice, 129 Strain, Biomarkers
Wellcome Trust (091484/Z/10/Z)
External DOI: https://doi.org/10.1038/ncb2965
This record's URL: https://www.repository.cam.ac.uk/handle/1810/292147