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Cell Rep. 2018 Jan 23;22(4):876-884. doi: 10.1016/j.celrep.2017.12.098. Epub 2018 Jan 28.

Nascent Induced Pluripotent Stem Cells Efficiently Generate Entirely iPSC-Derived Mice while Expressing Differentiation-Associated Genes.

Author information

1
Skirball Institute of Biomolecular Medicine, Department of Cell Biology and Helen L. and Martin S. Kimmel Center for Biology and Medicine, NYU School of Medicine, New York, NY 10016, USA.
2
Edward and Sandra Meyer Cancer Center and Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
3
Cytometry and Cell Sorting Laboratory, NYU School of Medicine, New York, NY 10016, USA.
4
Department of Pathology and Office for Collaborative Science, NYU School of Medicine, New York, NY 10016, USA.
5
Department of Pathology and Office for Collaborative Science, NYU School of Medicine, New York, NY 10016, USA. Electronic address: sang.kim@nyumc.org.
6
Skirball Institute of Biomolecular Medicine, Department of Cell Biology and Helen L. and Martin S. Kimmel Center for Biology and Medicine, NYU School of Medicine, New York, NY 10016, USA. Electronic address: matthias.stadtfeld@med.nyu.edu.

Abstract

The ability of induced pluripotent stem cells (iPSCs) to differentiate into all adult cell types makes them attractive for research and regenerative medicine; however, it remains unknown when and how this capacity is established. We characterized the acquisition of developmental pluripotency in a suitable reprogramming system to show that iPSCs prior to passaging become capable of generating all tissues upon injection into preimplantation embryos. The developmental potential of nascent iPSCs is comparable to or even surpasses that of established pluripotent cells. Further functional assays and genome-wide molecular analyses suggest that cells acquiring developmental pluripotency exhibit a unique combination of properties that distinguish them from canonical naive and primed pluripotency states. These include reduced clonal self-renewal potential and the elevated expression of differentiation-associated transcriptional regulators. Our observations close a gap in the understanding of induced pluripotency and provide an improved roadmap of cellular reprogramming with ramifications for the use of iPSCs.

KEYWORDS:

Otx2; developmental potential; iPSCs; pluripotency; reprogramming; tetraploid complementation

PMID:
29420174
PMCID:
PMC6664440
DOI:
10.1016/j.celrep.2017.12.098
[Indexed for MEDLINE]
Free PMC Article

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