期刊
STEM CELLS
卷 33, 期 2, 页码 378-391出版社
WILEY
DOI: 10.1002/stem.1871
关键词
Pluripotent stem cells; Accessible chromatin; Transcriptional regulation; Gene expression; Enhancers
资金
- Empire State Stem Cell Board grant through the New York State Department of Health (NYSTEM) [CO24322]
- NIH NCI [1T32CA160002]
Both pluripotent embryonic stem cells (ESCs), established from preimplantation murine blastocysts, and epiblast stem cells (EpiSCs), established from postimplantation embryos, can self-renew in culture or differentiate into each of the primary germ layers. While the core transcription factors (TFs) OCT4, SOX2, and NANOG are expressed in both cell types, the gene expression profiles and other features suggest that ESCs and EpiSCs reflect distinct developmental maturation stages of the epiblast in vivo. Accordingly, naive or ground state ESCs resemble cells of the inner cell mass, whereas primed EpiSCs resemble cells of the postimplantation egg cylinder. To gain insight into the relationship between naive and primed pluripotent cells, and of each of these pluripotent states to that of nonpluripotent cells, we have used FAIRE-seq to generate a comparative atlas of the accessible chromatin regions within ESCs, EpiSCs, multipotent neural stem cells, and mouse embryonic fibroblasts. We find a distinction between the accessible chromatin patterns of pluripotent and somatic cells that is consistent with the highly related phenotype of ESCs and EpiSCs. However, by defining cell-specific and shared regions of open chromatin, and integrating these data with published gene expression and ChIP analyses, we also illustrate unique features of the chromatin of naive and primed cells. Functional studies suggest that multiple stage-specific enhancers regulate ESC- or EpiSC-specific gene expression, and implicate auxiliary TFs as important modulators for stage-specific activation by the core TFs. Together these observations provide insights into the chromatin structure dynamics accompanying transitions between these pluripotent states.
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