Molecular Criteria for Defining the Naive Human Pluripotent State

Thorold W. Theunissen, Marc Friedli, Yupeng He, Evarist Planet, Ryan C. O'Neil, Styliani Markoulaki, Julien Pontis, Haoyi Wang, Alexandra Iouranova, Michaël Imbeault, Julien Duc, Malkiel A. Cohen, Katherine J. Wert, Rosa Castanon, Zhuzhu Zhang, Yanmei Huang, Joseph R. Nery, Jesse Drotar, Tenzin Lungjangwa, Didier Trono*Joseph R. Ecker, Rudolf Jaenisch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

348 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)502-515
Number of pages14
JournalCell stem cell
Issue number4
StatePublished - Oct 6 2016


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

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Cell Biology


Dive into the research topics of 'Molecular Criteria for Defining the Naive Human Pluripotent State'. Together they form a unique fingerprint.

Cite this