title: Lineage-Specific Profiling Delineates the Emergence and Progression of Naive Pluripotency in Mammalian Embryogenesis.
abstract: Naive pluripotency is manifest in the preimplantation mammalian embryo. Here we determine transcriptome dynamics of mouse development from the eight-cell stage to postimplantation using lineage-specific RNA sequencing. This method combines high sensitivity and reporter-based fate assignment to acquire the full spectrum of gene expression from discrete embryonic cell types. We define expression modules indicative of developmental state and temporal regulatory patterns marking the establishment and dissolution of naive pluripotency in vivo. Analysis of embryonic stem cells and diapaused embryos reveals near-complete conservation of the core transcriptional circuitry operative in the preimplantation epiblast. Comparison to inner cell masses of marmoset primate blastocysts identifies a similar complement of pluripotency factors but use of alternative signaling pathways. Embryo culture experiments further indicate that marmoset embryos utilize WNT signaling during early lineage segregation, unlike rodents. These findings support a conserved transcription factor foundation for naive pluripotency while revealing species-specific regulatory features of lineage segregation.
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Boroviak
authors.affiliation: European Bioinformatics Institute, European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK.
authors.forename: Remco
authors.initials: R
authors.lastname: Loos
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lombard
authors.affiliation: Department of Applied Developmental Biology, Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kanagawa 210-0821, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Okahara
authors.affiliation: Deutsches Primatenzentrum (German Primate Center), Leibniz-Institut für Primatenforschung, Kellnerweg 4, 37077 Göttingen, Germany; DZHK (German Center for Cardiovascular Research), Wilhelmsplatz 1, 37073 Göttingen, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Behr
authors.affiliation: Department of Applied Developmental Biology, Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kanagawa 210-0821, Japan; Keio Advanced Research Center, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Sasaki
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, Tennis Court Road, Cambridge CB2 3EG, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nichols
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; European Bioinformatics Institute, European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK; Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany. Electronic address: bertone@ebi.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Bertone
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics* / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005855:Germ Layers / Q000166:cytology*; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology*
keywords: diapause; embryonic stem cell; inner cell mass; pluripotency; primate