title: Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency.
abstract: Known molecular determinants of developmental plasticity are mainly transcription factors, while the extrinsic regulation of this process has been largely unexplored. Here we identify Cripto as one of the earliest epiblast markers and a key extracellular determinant of the naive and primed pluripotent states. We demonstrate that Cripto sustains mouse embryonic stem cell (ESC) self-renewal by modulating Wnt/β-catenin, whereas it maintains mouse epiblast stem cell (EpiSC) and human ESC pluripotency through Nodal/Smad2. Moreover, we provide unprecedented evidence that Cripto controls the metabolic reprogramming in ESCs to EpiSC transition. Remarkably, Cripto deficiency attenuates ESC lineage restriction in vitro and in vivo, and permits ESC transdifferentiation into trophectoderm lineage, suggesting that Cripto has earlier functions than previously recognized. All together, our studies provide novel insights into the current model of mammalian pluripotency and contribute to the understanding of the extrinsic regulation of the first cell lineage decision in the embryo.
authors: Stem Cell Fate Laboratory, Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Via Pietro Castellino 111, 80131 Naples, Italy.
authors: Alessandro
authors: A
authors: Fiorenzano
authors: Stem Cell Fate Laboratory, Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Via Pietro Castellino 111, 80131 Naples, Italy.
authors: Emilia
authors: E
authors: Pascale
authors: Stem Cell Fate Laboratory, Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Via Pietro Castellino 111, 80131 Naples, Italy.
authors: Cristina
authors: C
authors: D'Aniello
authors: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy.|IRCCS Neuromed, 860077 Pozzilli (IS), Italy.
authors: Dario
authors: D
authors: Acampora
authors: Inserm, UMR1103, F-63001; CNRS, UMR6293, F-63001; Université Clermont Auvergne, Laboratoire GReD, BP 10448, Clermont-Ferrand F-63000, France.
authors: Cecilia
authors: C
authors: Bassalert
authors: Institute for Applied Mathematics 'Mauro Picone', CNR, 80131, Naples, Italy.
authors: Francesco
authors: F
authors: Russo
authors: Stem Cell Fate Laboratory, Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Via Pietro Castellino 111, 80131 Naples, Italy.
authors: Gennaro
authors: G
authors: Andolfi
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome 00161, Italy.
authors: Mauro
authors: 0000-0002-1304-9060
authors: M
authors: Biffoni
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome 00161, Italy.
authors: Federica
authors: F
authors: Francescangeli
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome 00161, Italy.
authors: Ann
authors: A
authors: Zeuner
authors: Institute for Applied Mathematics 'Mauro Picone', CNR, 80131, Naples, Italy.
authors: Claudia
authors: 0000-0001-8350-8464
authors: C
authors: Angelini
authors: Inserm, UMR1103, F-63001; CNRS, UMR6293, F-63001; Université Clermont Auvergne, Laboratoire GReD, BP 10448, Clermont-Ferrand F-63000, France.
authors: Claire
authors: C
authors: Chazaud
authors: Stem Cell Fate Laboratory, Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Via Pietro Castellino 111, 80131 Naples, Italy.
authors: Eduardo J
authors: EJ
authors: Patriarca
authors: Stem Cell Fate Laboratory, Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Via Pietro Castellino 111, 80131 Naples, Italy.
authors: Annalisa
authors: A
authors: Fico
authors: Stem Cell Fate Laboratory, Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Via Pietro Castellino 111, 80131 Naples, Italy.
authors: Gabriella
authors: G
authors: Minchiotti
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics; D047108:Embryonic Development / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D005855:Germ Layers / Q000166:cytology; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D055457:Nodal Protein / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000502:physiology*; D051899:Smad2 Protein / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D055457:Nodal Protein; C526008:Nodal protein, mouse; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; C489450:Tdgf1 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin; D004815:Epidermal Growth Factor