Parallel derivation of isogenic human primed and naive induced pluripotent stem cells

Stéphanie Kilens 1 Dimitri Meistermann 1 Caroline Chariau 2 Anne Gaignerie 2 Arnaud Reignier 1 Yohann Lelièvre 3 Miguel Casanova 4 Céline Vallot 4 Steven Nedellec 2 Léa Flippe 1 Julie Firmin 1 Juan Song 5 Eric Charpentier 6 Jenna Lammers 1 Audrey Donnart 6 Nadège Marec 7 Wallid Deb 8 Audrey Bihouée 6 Milieu Intérieur Consortium Cédric Le Caignec 8, 9 Claire Pecqueur 10 Richard Redon 6 Paul Barriere 1 Jérémie Bourdon 3 Vincent Pasque 5 Magali Soumillon 11 Tarjei Mikkelsen 11 Claire Rougeulle 4 Thomas Freour 1 Laurent David 1 Laurent Abel 12 Andrès Alcover 13 Philippe Bousso 14 Pierre Bruhns 15 Ana Cumano 16 Darragh Duffy 17 Caroline Demangel 18 Ludovic Deriano 19 James Santo 20 Françoise Dromer 21 Gérard Eberl 22 Jost Enninga 23 Jacques Fellay 24 Antonio Freitas 25 Odile Gelpi 26 Ivo Gomperts Boneca 27 Serge Hercberg 28 Olivier Lantz 29 Claude Leclerc 30 Hugo Mouquet 31 Etienne Patin 32 Sandra Pellegrini 33 Stanislas Pol 34 Lars Rogge 35 Anavaj Sakuntabhai 36 Olivier Schwartz 37 Benno Schwikowski 32 Spencer Shorte 38 Vassili Soumelis 29 Frédéric Tangy 39 Eric Tartour 40 Antoine Toubert 41 Marie Noëlle Ungeheuer 42 Lluis Quintana-Murci 43 Matthew Albert 17
7 CRCINA – Unité Inserm U1232 - Plate-forme CytoCell [Nantes]
CRCINA - Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers
12 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
IMAGINE - U1163 - Imagine - Institut des maladies génétiques
28 CRESS - U1153 - Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle
UP13 - Université Paris 13, INRA - Institut National de la Recherche Agronomique, CNAM - Conservatoire National des Arts et Métiers [CNAM], CRESS (U1153 / UMR_A 1125) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité
Abstract : Induced pluripotent stem cells (iPSCs) have considerably impacted human developmental biology and regenerative medicine, notably because they circumvent the use of cells of embryonic origin and offer the potential to generate patient-specific pluripotent stem cells. However, conventional reprogramming protocols produce developmentally advanced, or primed, human iPSCs (hiPSCs), restricting their use to post-implantation human development modeling. Hence, there is a need for hiPSCs resembling preimplantation naive epiblast. Here, we develop a method to generate naive hiPSCs directly from somatic cells, using OKMS overexpression and specific culture conditions, further enabling parallel generation of their isogenic primed counterparts. We benchmark naive hiPSCs against human preimplantation epiblast and reveal remarkable concordance in their transcriptome, dependency on mito-chondrial respiration and X-chromosome status. Collectively, our results are essential for the understanding of pluripotency regulation throughout preimplantation development and generate new opportunities for disease modeling and regenerative medicine.
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Stéphanie Kilens, Dimitri Meistermann, Caroline Chariau, Anne Gaignerie, Arnaud Reignier, et al.. Parallel derivation of isogenic human primed and naive induced pluripotent stem cells. Nature Communications, Nature Publishing Group, 2018, 9 (1), pp.302 - 314. 〈10.1038/s41467-017-02107-w〉. 〈pasteur-01758726〉

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