不同类别的内源性逆转录病毒元件的动态转录标记了特定人群的早期人类胚胎细胞。

Dynamic transcription of distinct classes of endogenous retroviral elements marks specific populations of early human embryonic cells.

机构信息

Computational and Systems Biology, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.

Gene Regulation Laboratory, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.

出版信息

Cell Stem Cell. 2015 Feb 5;16(2):135-41. doi: 10.1016/j.stem.2015.01.005.

DOI:10.1016/j.stem.2015.01.005

PMID:25658370

Abstract

About half of the human genome consists of highly repetitive elements, most of which are considered dispensable for human life. Here, we report that repetitive elements originating from endogenous retroviruses (ERVs) are systematically transcribed during human early embryogenesis in a stage-specific manner. Our analysis highlights that the long terminal repeats (LTRs) of ERVs provide the template for stage-specific transcription initiation, thereby generating hundreds of co-expressed, ERV-derived RNAs. Conversion of human embryonic stem cells (hESCs) to an epiblast-like state activates blastocyst-specific ERV elements, indicating that their activity dynamically reacts to changes in regulatory networks. In addition to initiating stage-specific transcription, many ERV families contain preserved splice sites that join the ERV segment with non-ERV exons in their genomic vicinity. In summary, we find that ERV expression is a hallmark of cellular identity and cell potency that characterizes the cell populations in early human embryos.

摘要

人类基因组的大约一半由高度重复的元件组成，其中大多数被认为对人类生命是可有可无的。在这里，我们报告说，源自内源性逆转录病毒（ERV）的重复元件在人类早期胚胎发生中以特定于阶段的方式被系统转录。我们的分析强调，ERV 的长末端重复（LTR）为特定于阶段的转录起始提供了模板，从而产生数百个共表达的、ERV 衍生的 RNA。将人类胚胎干细胞（hESC）转化为类胚层状态会激活囊胚特异性 ERV 元件，这表明它们的活性会对调控网络的变化做出动态反应。除了启动特定于阶段的转录外，许多 ERV 家族还包含保存的剪接位点，这些剪接位点将 ERV 片段与它们基因组附近的非 ERV 外显子连接起来。总之，我们发现 ERV 的表达是细胞身份和细胞潜能的标志，这些标志特征描述了早期人类胚胎中的细胞群体。