Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass
von, Meyenn Ferdinand
Stem Cell Reports
Elsevier (Cell Press)
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Guo, G., von, M. F., Santos, F., Chen, Y., Reik, W., Bertone, P., Smith, A., & et al. (2016). Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass. Stem Cell Reports, 6 437-446. https://doi.org/10.1016/j.stemcr.2016.02.005
Conventional generation of stem cells from human blastocysts produces a developmentally advanced, or primed, stage of pluripotency. In vitro resetting to a more naive phenotype has been reported. However, whether the reset culture conditions of selective kinase inhibition can enable capture of naïve epiblast cells directly from the embryo has not been determined. Here we show that in these specific conditions individual inner cell mass cells grow into colonies that may then be expanded over multiple passages while retaining a diploid karyotype and naïve properties. The cells express hallmark naïve pluripotency factors and additionally display features of mitochondrial respiration, global gene expression and genome-wide hypomethylation distinct from primed cells. They transition through primed pluripotency into somatic lineage differentiation. Collectively these attributes suggest classification as human naïve embryonic stem (HNES) cells. Human counterparts of canonical mouse embryonic stem cells would argue for conservation in the phased progression of pluripotency in mammals.
naive pluripotency, human embryonic stem cell derivation, epiblast, inner cell mass, human blastocyst
This work was supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Swiss National Science Foundation (SNF)/Novartis SNF (F.v.M.) and core funding to the Cambridge Stem Cell Institute from the Wellcome Trust and Medical Research Council. AS is a Medical Research Council Professor.
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External DOI: https://doi.org/10.1016/j.stemcr.2016.02.005
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253776
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/