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Cell Stem Cell. 2016 Oct 6;19(4):502-515. doi: 10.1016/j.stem.2016.06.011. Epub 2016 Jul 14.

Molecular Criteria for Defining the Naive Human Pluripotent State.

Author information

1
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
2
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
3
Genomic Analysis Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Bioinformatics Program, University of California, San Diego, La Jolla, CA 92093, USA.
4
Genomic Analysis Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
5
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: didier.trono@epfl.ch.
6
Genomic Analysis Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: ecker@salk.edu.
7
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: jaenisch@wi.mit.edu.

Abstract

Recent studies have aimed to convert cultured human pluripotent cells to a naive state, but it remains unclear to what extent the resulting cells recapitulate in vivo naive pluripotency. Here we propose a set of molecular criteria for evaluating the naive human pluripotent state by comparing it to the human embryo. We show that transcription of transposable elements provides a sensitive measure of the concordance between pluripotent stem cells and early human development. We also show that induction of the naive state is accompanied by genome-wide DNA hypomethylation, which is reversible except at imprinted genes, and that the X chromosome status resembles that of the human preimplantation embryo. However, we did not see efficient incorporation of naive human cells into mouse embryos. Overall, the different naive conditions we tested showed varied relationships to human embryonic states based on molecular criteria, providing a backdrop for future analysis of naive human pluripotency.

KEYWORDS:

DNA methylation; X chromosome reactivation; embryonic stem cells; imprinting; mouse-human chimeras; pluripotency; transposable elements

Comment in

PMID:
27424783
PMCID:
PMC5065525
DOI:
10.1016/j.stem.2016.06.011
[Indexed for MEDLINE]
Free PMC Article

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