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. Rogers & 1 others Andras Nagy

Research output: Contribution to journalArticle

78 Citations (Scopus)

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

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Stem Cells
Germ Layers
Pluripotent Stem Cells
Endoderm
Ectoderm
Mesoderm
Embryonic Stem Cells
Epigenomics
Transcription Factors
Embryonic Structures
Fibroblasts
Phenotype

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Tonge, P. D., Corso, A. J., Monetti, C., Hussein, S. M. I., Puri, M. C., Michael, I. P., ... Nagy, A. (2014). Divergent reprogramming routes lead to alternative stem-cell states. Nature, 516(7530), 192-197. https://doi.org/10.1038/nature14047

Divergent reprogramming routes lead to alternative stem-cell states. / Tonge, Peter D.; Corso, Andrew J.; Monetti, Claudio; Hussein, Samer M I; Puri, Mira C.; Michael, Iacovos P.; Li, Mira; Lee, Dong Sung; Mar, Jessica C.; Cloonan, Nicole; Wood, David L.; Gauthier, Maely E.; Korn, Othmar; Clancy, Jennifer L.; Preiss, Thomas; Grimmond, Sean M.; Shin, Jong Yeon; Seo, Jeong Sun; Wells, Christine A.; Rogers, Ian M.; Nagy, Andras.

In: Nature, Vol. 516, No. 7530, 11.12.2014, p. 192-197.

Research output: Contribution to journalArticle

Tonge, PD, Corso, AJ, Monetti, C, Hussein, SMI, Puri, MC, Michael, IP, Li, M, Lee, DS, Mar, JC, Cloonan, N, Wood, DL, Gauthier, ME, Korn, O, Clancy, JL, Preiss, T, Grimmond, SM, Shin, JY, Seo, JS, Wells, CA, Rogers, IM & Nagy, A 2014, 'Divergent reprogramming routes lead to alternative stem-cell states', Nature, vol. 516, no. 7530, pp. 192-197. https://doi.org/10.1038/nature14047
Tonge PD, Corso AJ, Monetti C, Hussein SMI, Puri MC, Michael IP et al. Divergent reprogramming routes lead to alternative stem-cell states. Nature. 2014 Dec 11;516(7530):192-197. https://doi.org/10.1038/nature14047
Tonge, Peter D. ; Corso, Andrew J. ; Monetti, Claudio ; Hussein, Samer M I ; Puri, Mira C. ; Michael, Iacovos P. ; Li, Mira ; Lee, Dong Sung ; Mar, Jessica C. ; Cloonan, Nicole ; Wood, David L. ; Gauthier, Maely E. ; Korn, Othmar ; Clancy, Jennifer L. ; Preiss, Thomas ; Grimmond, Sean M. ; Shin, Jong Yeon ; Seo, Jeong Sun ; Wells, Christine A. ; Rogers, Ian M. ; Nagy, Andras. / Divergent reprogramming routes lead to alternative stem-cell states. In: Nature. 2014 ; Vol. 516, No. 7530. pp. 192-197.
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