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

Research output: Contribution to journalArticle

87 Citations (Scopus)

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

Fingerprint

Epigenomics
Mental Competency
Chromatin
Transcription Factors
Stem Cells
Endoderm
Aptitude
Cell Lineage
Transcriptional Activation
Embryonic Development
Cues
Human Embryonic Stem Cells
Liver

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Wang, Allen ; Yue, Feng ; Li, Yan ; Xie, Ruiyu ; Harper, Thomas ; Patel, Nisha A. ; Muth, Kayla ; Palmer, Jeffrey ; Qiu, Yunjiang ; Wang, Jinzhao ; Lam, Dieter K. ; Raum, Jeffrey C. ; Stoffers, Doris A. ; Ren, Bing ; Sander, Maike. / Epigenetic priming of enhancers predicts developmental competence of hESC-derived endodermal lineage intermediates. In: Cell Stem Cell. 2015 ; Vol. 16, No. 4. pp. 386-399.
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Wang, A, Yue, F, Li, Y, Xie, R, Harper, T, Patel, NA, Muth, K, Palmer, J, Qiu, Y, Wang, J, Lam, DK, Raum, JC, Stoffers, DA, Ren, B & Sander, M 2015, 'Epigenetic priming of enhancers predicts developmental competence of hESC-derived endodermal lineage intermediates', Cell Stem Cell, vol. 16, no. 4, pp. 386-399. https://doi.org/10.1016/j.stem.2015.02.013

Epigenetic priming of enhancers predicts developmental competence of hESC-derived endodermal lineage intermediates. / Wang, Allen; Yue, Feng; Li, Yan; Xie, Ruiyu; Harper, Thomas; Patel, Nisha A.; Muth, Kayla; Palmer, Jeffrey; Qiu, Yunjiang; Wang, Jinzhao; Lam, Dieter K.; Raum, Jeffrey C.; Stoffers, Doris A.; Ren, Bing; Sander, Maike.

In: Cell Stem Cell, Vol. 16, No. 4, 02.04.2015, p. 386-399.

Research output: Contribution to journalArticle

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AU - Muth, Kayla

AU - Palmer, Jeffrey

AU - Qiu, Yunjiang

AU - Wang, Jinzhao

AU - Lam, Dieter K.

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AU - Stoffers, Doris A.

AU - Ren, Bing

AU - Sander, Maike

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