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

Stéphanie Kilens, Dimitri Meistermann, Diego Moreno, Caroline Chariau, Anne Gaignerie, Arnaud Reignier, Yohann Lelièvre, Miguel Casanova, Céline Vallot, Steven Nedellec, Léa Flippe, Julie Firmin, Juan Song, Eric Charpentier, Jenna Lammers, Audrey Donnart, Nadège Marec, Wallid Deb, Audrey Bihouée, Cédric Le Caignec, Claire Pecqueur, Richard Redon, Paul Barrière, Jérémie Bourdon, Vincent Pasque, Magali Soumillon, Tarjei S. Mikkelsen, Claire Rougeulle, Thomas Fréour and Laurent David ()
Additional contact information
Stéphanie Kilens: Université de Nantes
Dimitri Meistermann: Université de Nantes
Diego Moreno: Université de Nantes
Caroline Chariau: iPSC Core Facility, Nantes, France; CNRS, UMS 3556, Nantes, France; Université de Nantes, Nantes, France; CHU Nantes
Anne Gaignerie: iPSC Core Facility, Nantes, France; CNRS, UMS 3556, Nantes, France; Université de Nantes, Nantes, France; CHU Nantes
Arnaud Reignier: Université de Nantes
Yohann Lelièvre: Université de Nantes
Miguel Casanova: Université Paris Diderot
Céline Vallot: Université Paris Diderot
Steven Nedellec: MicroPicell Core Facility, Nantes, France; CNRS, UMS 3556, Nantes, France; Université de Nantes, Nantes, France; CHU de Nantes
Léa Flippe: Université de Nantes
Julie Firmin: Université de Nantes
Juan Song: Leuven Stem Cell Institute
Eric Charpentier: Université de Nantes l’institut du thorax
Jenna Lammers: Université de Nantes
Audrey Donnart: Université de Nantes l’institut du thorax
Nadège Marec: Cytocell Core Facility, Nantes, France; CNRS, UMS 3556, Nantes, France; Université de Nantes, Nantes, France; CHU Nantes
Wallid Deb: Service de génétique médicale
Audrey Bihouée: Université de Nantes l’institut du thorax
Cédric Le Caignec: Service de génétique médicale
Claire Pecqueur: Université de Nantes
Richard Redon: Université de Nantes l’institut du thorax
Paul Barrière: Université de Nantes
Jérémie Bourdon: Université de Nantes
Vincent Pasque: Leuven Stem Cell Institute
Magali Soumillon: Harvard University, Cambridge, MA, 02138, USA; Broad Institute, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University
Tarjei S. Mikkelsen: Harvard University, Cambridge, MA, 02138, USA; Broad Institute, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University
Claire Rougeulle: Université Paris Diderot
Thomas Fréour: Université de Nantes
Laurent David: Université de Nantes

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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 mitochondrial 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.

Date: 2018
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DOI: 10.1038/s41467-017-02107-w

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