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Nat Commun. 2018 Jan 24;9(1):360. doi: 10.1038/s41467-017-02107-w.

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

Author information

1
Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.
2
Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
3
LabEx IGO "Immunotherapy, Graft, Oncology", Nantes, France.
4
Laboratoire des Sciences du Numérique de Nantes, LS2N, UMR CNRS 6004, Université de Nantes, Nantes, France.
5
INSERM UMS 016, SFR Francois Bonamy, iPSC Core Facility, Nantes, France; CNRS, UMS 3556, Nantes, France; Université de Nantes, Nantes, France; CHU Nantes, Nantes, France.
6
CHU Nantes, Service de Biologie de la Reproduction, Nantes, France.
7
Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216 CNRS, Université Paris Diderot, Paris, France.
8
INSERM UMS 016, SFR Francois Bonamy, MicroPicell Core Facility, Nantes, France; CNRS, UMS 3556, Nantes, France; Université de Nantes, Nantes, France; CHU de Nantes, Nantes, France.
9
KU Leuven-University of Leuven, Department of Development and Regeneration, Stem Cell Biology and Embryology Unit, Leuven Stem Cell Institute, Herestraat 49, B-3000, Leuven, Belgium.
10
INSERM UMR1087, CNRS UMR6291, Université de Nantes l'institut du thorax, Nantes, France.
11
INSERM, UMS 016, SFR Francois Bonamy, Cytocell Core Facility, Nantes, France; CNRS, UMS 3556, Nantes, France; Université de Nantes, Nantes, France; CHU Nantes, Nantes, France.
12
CHU Nantes, Service de génétique médicale, Nantes, France.
13
INSERM, UMR1238, Bone Sarcoma and Remodeling of Calcified Tissue, Nantes, France.
14
CRCINA, INSERM, Université de Nantes, Nantes, France.
15
CHU Nantes, l'institut du thorax, Nantes, France.
16
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, USA; Broad Institute, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, 02138, USA.
17
Berkeley Lights Inc., 5858 Horton Street, Emeryville, CA, 94608, USA.
18
10x Genomics, 7068 Koll Center Pkwy #401, Pleasanton, CA, 94566, USA.
19
Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France. Laurent.david@univ-nantes.fr.
20
Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France. Laurent.david@univ-nantes.fr.
21
LabEx IGO "Immunotherapy, Graft, Oncology", Nantes, France. Laurent.david@univ-nantes.fr.
22
INSERM UMS 016, SFR Francois Bonamy, iPSC Core Facility, Nantes, France; CNRS, UMS 3556, Nantes, France; Université de Nantes, Nantes, France; CHU Nantes, Nantes, France. Laurent.david@univ-nantes.fr.

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.

PMID:
29367672
PMCID:
PMC5783949
DOI:
10.1038/s41467-017-02107-w
[Indexed for MEDLINE]
Free PMC Article

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