title: Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass.
abstract: 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 naive 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 naive properties. The cells express hallmark naive 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 naive embryonic stem cells. Human counterparts of canonical mouse embryonic stem cells would argue for conservation in the phased progression of pluripotency in mammals.
authors.affiliation: Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Ge
authors.initials: G
authors.lastname: Guo
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: von Meyenn
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Fatima
authors.initials: F
authors.lastname: Santos
authors.affiliation: Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Wolf
authors.initials: W
authors.lastname: Reik
authors.affiliation: Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Bertone
authors.affiliation: Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK. Electronic address: austin.smith@cscr.cam.ac.uk.
authors.forename: Austin
authors.initials: A
authors.lastname: Smith
authors.affiliation: Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 4BG, UK. Electronic address: jn270@cam.ac.uk.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nichols
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D019175:DNA Methylation; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling / Q000379:methods; D005855:Germ Layers / Q000166:cytology* / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics