期刊
CELL STEM CELL
卷 16, 期 4, 页码 386-399出版社
CELL PRESS
DOI: 10.1016/j.stem.2015.02.013
关键词
-
资金
- NIH [U01-DK089567, U01-DK072473, U01-ES017166, U01-DK089540]
- California Institute for Regenerative Medicine (CIRM) [RB5-07236]
- Helmsley Charitable Trust [2012PG-T1D074, JDRF-3-2012-177, T32 DK7494-27]
- CIRM Bridges to Stem Cells Program
- [CIRM-TG201154]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据