Divergent reprogramming routes lead to alternative stem-cell states

Peter D. Tonge, Andrew J. Corso, Claudio Monetti, Samer M.I. Hussein, Mira C. Puri, Iacovos P. Michael, Mira Li, Dong Sung Lee, Jessica C. Mar, Nicole Cloonan, David L. Wood, Maely E. Gauthier, Othmar Korn, Jennifer L. Clancy, Thomas Preiss, Sean M. Grimmond, Jong Yeon Shin, Jeong Sun Seo, Christine A. Wells, Ian M. RogersAndras Nagy

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Pluripotency is defined by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluripotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluripotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique epigenetic modifications to arrive at a stable, Nanog-positive, alternative pluripotent state. In doing so, we prove that the pluripotent spectrum can encompass multiple, unique cell states.

Original languageEnglish (US)
Pages (from-to)192-197
Number of pages6
JournalNature
Volume516
Issue number7530
DOIs
StatePublished - Dec 11 2014

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Divergent reprogramming routes lead to alternative stem-cell states'. Together they form a unique fingerprint.

  • Cite this

    Tonge, P. D., Corso, A. J., Monetti, C., Hussein, S. M. I., Puri, M. C., Michael, I. P., Li, M., Lee, D. S., Mar, J. C., Cloonan, N., Wood, D. L., Gauthier, M. E., Korn, O., Clancy, J. L., Preiss, T., Grimmond, S. M., Shin, J. Y., Seo, J. S., Wells, C. A., ... Nagy, A. (2014). Divergent reprogramming routes lead to alternative stem-cell states. Nature, 516(7530), 192-197. https://doi.org/10.1038/nature14047