Intersection clock reveals a rejuvenation event during human embryogenesis.
Intersection clock reveals a rejuvenation event during human embryogenesis.
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作者：
最近的研究揭示了小鼠早期发育过程中的返老还童事件。在这里，通过检查人类胚胎发生的表观遗传年龄动态，我们测试了人类中是否存在类似的事件。为此，我们开发了一种表观遗传时钟方法，即交叉时钟，该方法利用亚硫酸氢盐测序，最大限度地利用信息丰富的 CpG 位点，并且在测试样本中不丢失时钟 CpG 位点，并将其应用于人类胚胎发育数据。我们观察到卵裂期和囊胚期胚胎之间的预测表观遗传年龄没有变化；然而，在囊胚和代表外胚层的细胞之间观察到显着减少。此外，通过将交叉时钟应用于植入前和植入后的数据集，我们发现植入前阶段的表观遗传年龄没有显着变化；然而，与植入前阶段相比，植入后样本的表观遗传年龄较低。我们进一步研究了引发（代表植入后早期）和幼稚（代表植入前）多能干细胞的表观遗传年龄，并观察到在所有情况下，引发细胞的表观遗传年龄均显着低于幼稚细胞。总之，我们的数据表明人类胚胎在早期胚胎发生过程中恢复活力。因此，返老还童事件在小鼠和人类之间是保守的，并且它发生在两个物种的原肠胚阶段左右。除了这一进步之外，交叉时钟还为基于人类亚硫酸氢盐测序数据集而不是甲基化阵列的其他表观遗传年龄研究开辟了道路。我们开发了一种表观遗传时钟方法，即交叉时钟，它利用亚硫酸氢盐测序，最大限度地利用信息丰富的 CpG 位点，并且在测试样本中不会丢失时钟 CpG 位点。使用新方法，我们揭示了人类胚胎发生过程中原肠胚形成阶段的返老还童事件。交叉时钟为基于人类亚硫酸氢盐测序数据集的其他表观遗传年龄研究开辟了道路。
Recent research revealed a rejuvenation event during early development of mice. Here, by examining epigenetic age dynamics of human embryogenesis, we tested whether a similar event exists in humans. For this purpose, we developed an epigenetic clock method, the intersection clock, that utilizes bisulfite sequencing in a way that maximizes the use of informative CpG sites with no missing clock CpG sites in test samples and applied it to human embryo development data. We observed no changes in the predicted epigenetic age between cleavage stage and blastocyst stage embryos; however, a significant decrease was observed between blastocysts and cells representing the epiblast. Additionally, by applying the intersection clock to datasets spanning pre and postimplantation, we found no significant change in the epigenetic age during preimplantation stages; however, the epigenetic age of postimplantation samples was lower compared to the preimplantation stages. We further investigated the epigenetic age of primed (representing early postimplantation) and naïve (representing preimplantation) pluripotent stem cells and observed that in all cases the epigenetic age of primed cells was significantly lower than that of naïve cells. Together, our data suggest that human embryos are rejuvenated during early embryogenesis. Hence, the rejuvenation event is conserved between the mouse and human, and it occurs around the gastrulation stage in both species. Beyond this advance, the intersection clock opens the way for other epigenetic age studies based on human bisulfite sequencing datasets as opposed to methylation arrays. We developed an epigenetic clock method, the intersection clock, that utilizes bisulfite sequencing in a way that maximizes the use of informative CpG sites with no missing clock CpG sites in test samples. Using the new method, we revealed a rejuvenation event during human embryogenesis around the gastrulation stage. The intersection clock opens the way for other epigenetic age studies based on human bisulfite sequencing datasets.
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影响因子：
5.9
作者：
Guo G;von Meyenn F;Santos F;Chen Y;Reik W;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
64.5
作者：
Takashima Y;Guo G;Loos R;Nichols J;Ficz G;Krueger F;Oxley D;Santos F;Clarke J;Mansfield W;Reik W;Bertone P;Smith A
通讯作者：
Smith A
DOI：
10.18632/aging.100908
发表时间：
2016-02
期刊：
Aging
影响因子：
--
作者：
Lin Q;Weidner CI;Costa IG;Marioni RE;Ferreira MR;Deary IJ;Wagner W
通讯作者：
Wagner W
影响因子：
5.7
作者：
Breitling LP;Saum KU;Perna L;Schöttker B;Holleczek B;Brenner H
通讯作者：
Brenner H