Nucleosome organizations in induced pluripotent stem cells reprogrammed from somatic cells belonging to three different germ layers
Nucleosome organizations in induced pluripotent stem cells reprogrammed from somatic cells belonging to three different germ layers
复制标题
由属于三个不同胚层的体细胞重编程的诱导多能干细胞中的核小体组织
DOI：
10.1186/s12915-014-0109-x
复制
发表时间：
2014-11-21
期刊：
影响因子：
5.4
通讯作者：
Gao, Shaorong
中科院分区：
文献类型：
--
作者：
Tao, Yu;Zheng, Weisheng;Gao, Shaorong
背景核小体组织决定染色质状态，进而控制基因表达或沉默。核小体重塑发生在体细胞重编程过程中，但仍不清楚诱导多能干细胞 (iPSC) 重建的核小体组织与胚胎干细胞 (ESC) 的相似程度，以及 iPSC 是否继承了亲代成纤维细胞的一些残留基因表达。结果我们在小鼠 ESC 和从属于三个不同胚层的体细胞重编程的 iPSC 中生成了全基因组核小体图谱二次重编程系统。成对比较表明，无论 iPSC 的组织来源如何，iPSC 中的核小体组织与 ESC 几乎相同，但与小鼠胚胎成纤维细胞 (MEF) 不同。在活性基因的转录起始位点周围存在典型的核小体排列：-1、核小体耗尽区、+1、+2、+3 等核小体，而只有一个核小体占据沉默转录单位。转录因子结合位点具有特征性的核小体结构，因此它们的访问受到核小体的旋转和平移设置的控制。有趣的是，在重编程之前，组织特异性基因仅在相应 iPS 细胞系的亲本体细胞中高度表达，但在所有所得 iPSC 和 ESC 中具有相似的表达水平。 结论 核重编程过程中重新建立的核小体景观为小鼠多能干细胞中 DNA 序列的可及性提供了保守的环境。没有反映其组织来源的亲代体细胞的持久残留表达程序或核小体定位被传递到所得的小鼠 iPSC 上。
BackgroundNucleosome organization determines the chromatin state, which in turn controls gene expression or silencing. Nucleosome remodeling occurs during somatic cell reprogramming, but it is still unclear to what degree the re-established nucleosome organization of induced pluripotent stem cells (iPSCs) resembles embryonic stem cells (ESCs), and whether the iPSCs inherit some residual gene expression from the parental fibroblast cells.ResultsWe generated genome-wide nucleosome maps in mouse ESCs and in iPSCs reprogrammed from somatic cells belonging to three different germ layers using a secondary reprogramming system. Pairwise comparisons showed that the nucleosome organizations in the iPSCs, regardless of the iPSCs’ tissue of origin, were nearly identical to the ESCs, but distinct from mouse embryonic fibroblasts (MEF). There is a canonical nucleosome arrangement of -1, nucleosome depletion region, +1, +2, +3, and so on nucleosomes around the transcription start sites of active genes whereas only a nucleosome occupies silent transcriptional units. Transcription factor binding sites possessed characteristic nucleosomal architecture, such that their access was governed by the rotational and translational settings of the nucleosome. Interestingly, the tissue-specific genes were highly expressed only in the parental somatic cells of the corresponding iPS cell line before reprogramming, but had a similar expression level in all the resultant iPSCs and ESCs.ConclusionsThe re-established nucleosome landscape during nuclear reprogramming provides a conserved setting for accessibility of DNA sequences in mouse pluripotent stem cells. No persistent residual expression program or nucleosome positioning of the parental somatic cells that reflected their tissue of origin was passed on to the resulting mouse iPSCs.