Epigenetic priming of enhancers predicts developmental competence of hESC-derived endodermal lineage intermediates

Allen Wang, Feng Yue, Yan Li, Ruiyu Xie, Thomas Harper, Nisha A. Patel, Kayla Muth, Jeffrey Palmer, Yunjiang Qiu, Jinzhao Wang, Dieter K. Lam, Jeffrey C. Raum, Doris A. Stoffers, Bing Ren*, Maike Sander

*Corresponding author for this work

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

Embryonic development relies on the capacity of progenitor cells to appropriately respond to inductive cues, a cellular property known as developmental competence. Here, we report that epigenetic priming of enhancers signifies developmental competence during endodermal lineage diversification. Chromatin mapping during pancreatic and hepatic differentiation of human embryonic stem cells revealed the en masse acquisition of a poised chromatin state at enhancers specific to endoderm-derived cell lineages in gut tube intermediates. Experimentally, the acquisition of this poised enhancer state predicts the ability of endodermal intermediates to respond to inductive signals. Furthermore, these enhancers are first recognized by the pioneer transcription factors FOXA1 and FOXA2 when competence is acquired, while subsequent recruitment of lineage-inductive transcription factors, such as PDX1, leads to enhancer and target gene activation. Together, our results identify the acquisition of a poised chromatin state at enhancers as a mechanism by which progenitor cells acquire developmental competence.

Original languageEnglish (US)
Pages (from-to)386-399
Number of pages14
JournalCell stem cell
Volume16
Issue number4
DOIs
StatePublished - Apr 2 2015

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Wang, A., Yue, F., Li, Y., Xie, R., Harper, T., Patel, N. A., Muth, K., Palmer, J., Qiu, Y., Wang, J., Lam, D. K., Raum, J. C., Stoffers, D. A., Ren, B., & Sander, M. (2015). Epigenetic priming of enhancers predicts developmental competence of hESC-derived endodermal lineage intermediates. Cell stem cell, 16(4), 386-399. https://doi.org/10.1016/j.stem.2015.02.013