Human embryonic genome activation initiates at the one-cell stage.
Human embryonic genome activation initiates at the one-cell stage.
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DOI：
10.1016/j.stem.2021.11.012
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发表时间：
2022-02-03
期刊：
影响因子：
23.9
通讯作者：
Perry ACF
中科院分区：
文献类型：
--
作者：
Asami M;Lam BYH;Ma MK;Rainbow K;Braun S;VerMilyea MD;Yeo GSH;Perry ACF
在人类胚胎中，转录的起始（胚胎基因组激活[EGA]）发生在八细胞阶段，但其确切的时间和轮廓尚不清楚。为了解决这个问题，我们分析了人类中期II卵母细胞和双原核（2PN）单细胞胚胎中的基因表达。高分辨率单细胞RNA测序揭示了以前无法获得的卵母细胞到胚胎的基因表达变化。这证实了受精后的转录物耗尽（母体RNA降解），但也发现了数百个剪接转录物的低幅度上调。基因表达分析预测了胚胎过程，包括细胞周期进程和染色体维持以及转录激活因子，包括癌症相关基因调节因子。在异常的多原核（1PN）和三原核（3PN）单细胞胚胎中，转录被破坏。这些发现表明，人类胚胎转录起始于单细胞阶段，比以前认为的要早。基因上调的模式有望阐明人类发育开始时所涉及的过程，并对表观遗传、干细胞衍生的胚胎和癌症产生影响。基因表达起始于人类胚胎的单细胞阶段表达量很低，但在八细胞阶段之前一直保持升高上调的转录本被剪接并对应于胚胎过程在形态异常的单细胞胚胎中上调被破坏基因何时在新形成的人类胚胎中首次活跃尚不清楚。Asami和他的同事表明，这种活动在受精后不久就开始了，在单细胞阶段。基因激活反映了早期胚胎过程，在异常胚胎中被破坏，并预测与癌症相关的转录调节因子的联系。
In human embryos, the initiation of transcription (embryonic genome activation [EGA]) occurs by the eight-cell stage, but its exact timing and profile are unclear. To address this, we profiled gene expression at depth in human metaphase II oocytes and bipronuclear (2PN) one-cell embryos. High-resolution single-cell RNA sequencing revealed previously inaccessible oocyte-to-embryo gene expression changes. This confirmed transcript depletion following fertilization (maternal RNA degradation) but also uncovered low-magnitude upregulation of hundreds of spliced transcripts. Gene expression analysis predicted embryonic processes including cell-cycle progression and chromosome maintenance as well as transcriptional activators that included cancer-associated gene regulators. Transcription was disrupted in abnormal monopronuclear (1PN) and tripronuclear (3PN) one-cell embryos. These findings indicate that human embryonic transcription initiates at the one-cell stage, sooner than previously thought. The pattern of gene upregulation promises to illuminate processes involved at the onset of human development, with implications for epigenetic inheritance, stem-cell-derived embryos, and cancer. Gene expression initiates at the one-cell stage in human embryos Expression is of low magnitude but remains elevated until the eight-cell stage Upregulated transcripts are spliced and correspond to embryonic processes Upregulation is disrupted in morphologically abnormal one-cell embryos It is not known when genes are first active in newly formed human embryos. Asami and colleagues show that this activity begins soon after fertilization, at the one-cell stage. Gene activation mirrors early embryonic processes, is disrupted in abnormal embryos, and predicts links to cancer-associated transcription regulators.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4
作者：
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通讯作者：
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DOI：
10.1038/s41580-020-0215-2
发表时间：
2020-05
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Baluapuri A;Wolf E;Eilers M
通讯作者：
Eilers M
影响因子：
48
作者：
Katz, Yarden;Wang, Eric T.;Airoldi, Edoardo M.;Burge, Christopher B.
通讯作者：
Burge, Christopher B.
影响因子：
2.5
作者：
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通讯作者：
Aoki, F