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

Stéphanie Kilens (1, 2, 3) , Dimitri Meistermann (1, 2, 3, 4) , Diego Moreno (1, 2, 3) , Caroline Chariau (5) , Anne Gaignerie (5) , Arnaud Reignier (1, 2, 3, 6) , Yohann Lelièvre (4) , Miguel Casanova (7) , Céline Vallot (7) , Steven Nedellec (5) , Léa Flippe (1, 2, 3) , Julie Firmin (1, 2, 3, 6) , Juan Song (8) , Eric Charpentier (9) , Jenna Lammers (1, 2, 3, 6) , Audrey Donnart (9) , Nadège Marec (5) , Wallid Deb (10) , Audrey Bihouée (9) , Cédric Le Caignec (10, 11) , Claire Pecqueur (12) , Richard Redon (9, 6) , Paul Barriere (1, 2, 3, 6) , Jérémie Bourdon (4) , Vincent Pasque (8) , Magali Soumillon (13) , Tarjei Mikkelsen (13) , Claire Rougeulle (7) , Thomas Freour (1, 2, 3, 6) , Laurent David (1, 2, 3, 5) , Milieu Intérieur Consortium

1 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
2 ITUN - Institut de transplantation urologie-néphrologie
3 LabEX IGO Immunothérapie Grand Ouest
4 LS2N - Laboratoire des Sciences du Numérique de Nantes
5 SFR François Bonamy - Structure fédérative de recherche François Bonamy
6 CHU Nantes - Centre hospitalier universitaire de Nantes
7 EDC - Centre épigénétique et destin cellulaire
8 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven
9 ITX-lab - Unité de recherche de l'institut du thorax
10 Service de génétique médicale - Unité de génétique clinique [Nantes]
11 Phy-Os - Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238]
12 CRCINA-ÉQUIPE 14 - Endothelium Radiobiology and Targeting
13 BROAD INSTITUTE - Broad Institute of MIT and Harvard

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.

Domains: Quantitative Methods [q-bio.QM]; Human genetics; Innate immunity; Adaptive immunology; Populations and Evolution [q-bio.PE]; Infectious diseases

Stéphanie Kilens, Dimitri Meistermann, Diego Moreno, Caroline Chariau, Anne Gaignerie, et al.. Parallel derivation of isogenic human primed and naive induced pluripotent stem cells. Nature Communications, 2018, 9 (1), pp.302 - 314. ⟨10.1038/s41467-017-02107-w⟩. ⟨pasteur-01758726⟩