OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation

Zoltan Simandi, Attila Horvath, Lyndsey C. Wright, Ixchelt Cuaranta-Monroy, Isabella De Luca, Katalin Karolyi, Sascha Sauer, Jean Francois Deleuze, Lorraine J. Gudas, Shaun M. Cowley, L. Nagy

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Cell type specification relies on the capacity of undifferentiated cells to properly respond to specific differentiation-inducing signals. Using genomic approaches along with loss- and gain-of-function genetic models, we identified OCT4-dependent mechanisms that provide embryonic stem cells with the means to customize their response to external cues. OCT4 binds a large set of low-accessible genomic regions. At these sites, OCT4 is required for proper enhancer and gene activation by recruiting co-regulators and RAR:RXR or β-catenin, suggesting an unexpected collaboration between the lineage-determining transcription factor and these differentiation-initiating, signal-dependent transcription factors. As a proof of concept, we demonstrate that overexpression of OCT4 in a kidney cell line is sufficient for signal-dependent activation of otherwise unresponsive genes in these cells. Our results uncover OCT4 as an integral and necessary component of signal-regulated transcriptional processes required for tissue-specific responses.

Original languageEnglish
Pages (from-to)647-661
Number of pages15
JournalMolecular Cell
Volume63
Issue number4
DOIs
Publication statusPublished - Aug 18 2016

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Transcription Factors
Catenins
Genetic Models
Embryonic Stem Cells
Transcriptional Activation
Cues
Kidney
Cell Line
Genes

Keywords

  • Cdx1
  • embryonic stem cell
  • Hoxb1
  • Oct4
  • RAR:RXR
  • retinoic acid
  • Wnt/β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Simandi, Z., Horvath, A., Wright, L. C., Cuaranta-Monroy, I., De Luca, I., Karolyi, K., ... Nagy, L. (2016). OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation. Molecular Cell, 63(4), 647-661. https://doi.org/10.1016/j.molcel.2016.06.039

OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation. / Simandi, Zoltan; Horvath, Attila; Wright, Lyndsey C.; Cuaranta-Monroy, Ixchelt; De Luca, Isabella; Karolyi, Katalin; Sauer, Sascha; Deleuze, Jean Francois; Gudas, Lorraine J.; Cowley, Shaun M.; Nagy, L.

In: Molecular Cell, Vol. 63, No. 4, 18.08.2016, p. 647-661.

Research output: Contribution to journalArticle

Simandi, Z, Horvath, A, Wright, LC, Cuaranta-Monroy, I, De Luca, I, Karolyi, K, Sauer, S, Deleuze, JF, Gudas, LJ, Cowley, SM & Nagy, L 2016, 'OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation', Molecular Cell, vol. 63, no. 4, pp. 647-661. https://doi.org/10.1016/j.molcel.2016.06.039
Simandi Z, Horvath A, Wright LC, Cuaranta-Monroy I, De Luca I, Karolyi K et al. OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation. Molecular Cell. 2016 Aug 18;63(4):647-661. https://doi.org/10.1016/j.molcel.2016.06.039
Simandi, Zoltan ; Horvath, Attila ; Wright, Lyndsey C. ; Cuaranta-Monroy, Ixchelt ; De Luca, Isabella ; Karolyi, Katalin ; Sauer, Sascha ; Deleuze, Jean Francois ; Gudas, Lorraine J. ; Cowley, Shaun M. ; Nagy, L. / OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation. In: Molecular Cell. 2016 ; Vol. 63, No. 4. pp. 647-661.
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