Tracing the derivation of embryonic stem cells from the inner cell mass by single-cell RNA-Seq analysis.
Tracing the derivation of embryonic stem cells from the inner cell mass by single-cell RNA-Seq analysis.
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DOI：
10.1016/j.stem.2010.03.015
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发表时间：
2010-05-07
期刊：
影响因子：
23.9
通讯作者：
Surani MA
中科院分区：
文献类型：
--
作者：
Tang F;Barbacioru C;Bao S;Lee C;Nordman E;Wang X;Lao K;Surani MA
在从囊胚的内细胞团（ICM）细胞向体外多能胚胎干细胞（ESC）的转变过程中，正常的发育程序被获得无限自我更新和多能性能力的细胞所取代。我们通过在单细胞分辨率下使用RNA-Seq转录组分析来探索这种开关的潜在机制。我们检测到显着的分子转换和转录变体的主要变化，其中包括一般代谢的基因。此外，抑制性表观遗传调节因子的表达增加，同时基因激活因子减少，这可能是维持胚胎干细胞固有可塑性所必需的。此外，我们检测到microRNAs（miRNAs）的变化，其中一组靶向早期分化基因，而另一组靶向多能性基因以维持独特的ESC表观基因型。这种遗传和表观遗传事件可能有助于在包括癌症在内的患病组织形成期间从成人细胞的正常发育程序转换。在ICM到ESC过程中的单细胞RNA-Seq分析揭示了分子开关增强的抑制性表观遗传因子可能维持ESC表观基因型miRNA靶向分化和多能性mRNA的变化ESC形成过程中增强的代谢转录变体和基因
During the transition from the inner cell mass (ICM) cells of blastocysts to pluripotent embryonic stem cells (ESCs) in vitro, a normal developmental program is replaced in cells that acquire a capacity for infinite self-renewal and pluripotency. We explored the underlying mechanism of this switch by using RNA-Seq transcriptome analysis at the resolution of single cells. We detected significant molecular transitions and major changes in transcript variants, which include genes for general metabolism. Furthermore, the expression of repressive epigenetic regulators increased with a concomitant decrease in gene activators that might be necessary to sustain the inherent plasticity of ESCs. Furthermore, we detected changes in microRNAs (miRNAs), with one set that targets early differentiation genes while another set targets pluripotency genes to maintain the unique ESC epigenotype. Such genetic and epigenetic events may contribute to a switch from a normal developmental program in adult cells during the formation of diseased tissues, including cancers. ► Single-cell RNA-Seq analysis during ICM to ESC reveals molecular switches ► Enhanced repressive epigenetic factors may sustain ESC epigenotype ► Changes in miRNAs targets differentiation and pluripotency mRNAs ► Transcript variants and genes for metabolism enhanced during ESC formation
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