Transcriptional and epigenetic dynamics during specification of human embryonic stem cells.
Transcriptional and epigenetic dynamics during specification of human embryonic stem cells.
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DOI：
10.1016/j.cell.2013.04.037
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发表时间：
2013-05-23
期刊：
影响因子：
64.5
通讯作者：
Meissner A
中科院分区：
文献类型：
--
作者：
Gifford CA;Ziller MJ;Gu H;Trapnell C;Donaghey J;Tsankov A;Shalek AK;Kelley DR;Shishkin AA;Issner R;Zhang X;Coyne M;Fostel JL;Holmes L;Meldrim J;Guttman M;Epstein C;Park H;Kohlbacher O;Rinn J;Gnirke A;Lander ES;Bernstein BE;Meissner A
人类胚胎干细胞（HESC）的分化提供了一个独特的机会，可以研究促进人类环境中细胞过渡的调节机制。为此，我们通过代表三个胚胎细菌层中每一个的hESC分化而得出的人群进行了全面的转录和表观遗传分析。整个基因组亚硫酸盐测序，染色质免疫沉淀 - 测序和RNA测序的整合揭示了与每个谱系的规范相关的独特事件。 DNA甲基化和H3K4ME1的动态变化在被假定的远端调节元件上显而易见，或在特定谱系中激活。此外，我们确定了在未分化状态下表现出高DNA甲基化的位点的生殖层特异性H3K27me3富集。对这些初始规范事件的更好理解将有助于在当前方法中识别缺陷，从而导致更加忠实的差异化策略，并为细胞过渡期间人类监管程序的重新布线提供见解。
Differentiation of human embryonic stem cells (hESCs) provides a unique opportunity to study the regulatory mechanisms that facilitate cellular transitions in a human context. To that end, we performed comprehensive transcriptional and epigenetic profiling of populations derived through directed differentiation of hESCs representing each of the three embryonic germ layers. Integration of whole genome bisulfite sequencing, chromatin immunoprecipitation-sequencing and RNA-sequencing reveals unique events associated with specification towards each lineage. Dynamic alterations in DNA methylation and H3K4me1 are evident at putative distal regulatory elements bound by pluripotency factors or activated in specific lineages. In addition, we identified germ layer-specific H3K27me3 enrichment at sites exhibiting high DNA methylation in the undifferentiated state. A better understanding of these initial specification events will facilitate identification of deficiencies in current approaches leading to more faithful differentiation strategies as well as provide insights into the rewiring of human regulatory programs during cellular transitions.
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