Nature communications · 2018
Parallel derivation of isogenic human primed and naive induced pluripotent stem cells.
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Kilens Stéphanie, Meistermann Dimitri, Moreno Diego, Chariau Caroline, Gaignerie Anne, Reignier Arnaud, Lelièvre Yohann, Casanova Miguel, Vallot Céline, Nedellec Steven, Flippe Léa, Firmin Julie, Song Juan, Charpentier Eric, Lammers Jenna, Donnart Audrey, Marec Nadège, Deb Wallid, Bihouée Audrey, Le Caignec Cédric, Pecqueur Claire, Redon Richard, Barrière Paul, Bourdon Jérémie, Pasque Vincent, Soumillon Magali, Mikkelsen Tarjei S, Rougeulle Claire, Fréour Thomas, David Laurent, Milieu Intérieur Consortium
Аннотация
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.