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

Author

Listed:
  • Stéphanie Kilens

    (Université de Nantes
    CHU Nantes
    LabEx IGO “Immunotherapy, Graft, Oncology”)

  • Dimitri Meistermann

    (Université de Nantes
    CHU Nantes
    LabEx IGO “Immunotherapy, Graft, Oncology”
    Université de Nantes)

  • Diego Moreno

    (Université de Nantes
    CHU Nantes
    LabEx IGO “Immunotherapy, Graft, Oncology”)

  • 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
    CHU Nantes
    LabEx IGO “Immunotherapy, Graft, Oncology”
    Service de Biologie de la Reproduction)

  • 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
    CHU Nantes
    LabEx IGO “Immunotherapy, Graft, Oncology”)

  • Julie Firmin

    (Université de Nantes
    CHU Nantes
    LabEx IGO “Immunotherapy, Graft, Oncology”
    Service de Biologie de la Reproduction)

  • Juan Song

    (Leuven Stem Cell Institute)

  • Eric Charpentier

    (Université de Nantes l’institut du thorax)

  • Jenna Lammers

    (Université de Nantes
    CHU Nantes
    LabEx IGO “Immunotherapy, Graft, Oncology”
    Service de Biologie de la Reproduction)

  • 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
    UMR1238, Bone Sarcoma and Remodeling of Calcified Tissue)

  • Claire Pecqueur

    (Université de Nantes)

  • Richard Redon

    (Université de Nantes l’institut du thorax
    l’institut du thorax)

  • Paul Barrière

    (Université de Nantes
    CHU Nantes
    LabEx IGO “Immunotherapy, Graft, Oncology”
    Service de Biologie de la Reproduction)

  • 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
    Berkeley Lights Inc.)

  • Tarjei S. Mikkelsen

    (Harvard University, Cambridge, MA, 02138, USA; Broad Institute, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University
    10x Genomics)

  • Claire Rougeulle

    (Université Paris Diderot)

  • Thomas Fréour

    (Université de Nantes
    CHU Nantes
    LabEx IGO “Immunotherapy, Graft, Oncology”
    Service de Biologie de la Reproduction)

  • Laurent David

    (Université de Nantes
    CHU Nantes
    LabEx IGO “Immunotherapy, Graft, Oncology”
    iPSC Core Facility, Nantes, France; CNRS, UMS 3556, Nantes, France; Université de Nantes, Nantes, France; CHU Nantes)

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.

Suggested Citation

  • Stéphanie Kilens & Dimitri Meistermann & Diego Moreno & Caroline Chariau & Anne Gaignerie & Arnaud Reignier & Yohann Lelièvre & Miguel Casanova & Céline Vallot & Steven Nedellec & Léa Flippe & Julie F, 2018. "Parallel derivation of isogenic human primed and naive induced pluripotent stem cells," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02107-w
    DOI: 10.1038/s41467-017-02107-w
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