Dissecting the molecular features of bovine-arrested eight-cell embryos using single-cell multi-omics sequencing
Dissecting the molecular features of bovine-arrested eight-cell embryos using single-cell multi-omics sequencing
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利用单细胞多组学测序剖析牛停滞的八细胞胚胎的分子特征
DOI：
10.1093/biolre/ioad038
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发表时间：
2023-03
影响因子：
3.6
通讯作者：
Jingyao Zhang;Qingji Lyu;Jing Li;Zhuoran Ma;Ruoyu Yang;Xunzhe Yin;Lei Yang;Shuai Gao
中科院分区：
文献类型：
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作者：
Jingyao Zhang;Qingji Lyu;Jing Li;Zhuoran Ma;Ruoyu Yang;Xunzhe Yin;Lei Yang;Shuai Gao
哺乳动物早期胚胎发育的调控是一个复杂的协调过程，涉及广泛的转录组和表观遗传重塑。体外受精后着床前胚胎发育失败的主要原因是不可逆的卵裂阻滞阶段。为了加深我们对这种胚胎阻滞的理解，我们绘制了拷贝数变异（CNVs）、转录组、DNA甲基组和染色质状态的单细胞多组学图谱，这些胚胎具有两细胞命运，要么停滞，要么发育成囊胚。为了做到这一点，我们对活检后的卵裂球进行了测序，并追踪了剩余细胞的发育潜力。通过DNA和rna文库数据推断的非整倍体胚胎往往会失去其发育潜能。对DNA甲基化和染色质可及性的不同基因组区域的分析表明，与囊胚发育的整倍体8细胞胚胎相比，阻滞的整倍体8细胞胚胎的基因功能和信号通路（如MAPK信号通路）的富集发生了改变。此外，胚胎基因组激活相关基因的RNA表达和染色质可及性在被抑制的整倍体胚胎中低于囊胚发育胚胎。综上所述，我们的研究结果表明，8细胞胚胎的发育障碍可能是由多个分子层引起的，包括CNVs、DNA甲基化和染色质可及性异常、胚胎基因组激活相关基因表达不足等。我们的综合和全面的数据集提供了一个宝贵的资源，以进一步剖析牛八细胞胚胎在体外捕获的确切机制。单细胞活检和组学技术表明，牛8细胞胚胎的体外捕获涉及多方面的挑战，包括CNVs、DNA甲基化和染色质可及性异常、EGA基因表达不足等。图形摘要https://tidbitapp.io/tidbits/dissecting-the-molecular-features-of-bovine-arrested-eight-cell-embryos-using-single-cell-multi-omics-sequencing-9ea06d4e-2288-4849-9969-4eb6d13e80cf
Abstract The regulation of mammalian early-embryonic development is a complex, coordinated process that involves widespread transcriptomic and epigenetic remodeling. The main cause of developmental failure in preimplantation embryos after in vitro fertilization is the irreversible arrested-at-cleavage stage. To deepen our understanding of this embryonic block, we profiled a single-cell multi-omics map of copy number variations (CNVs), the transcriptome, the DNA methylome, and the chromatin state of bovine eight-cell embryos with a two-cell fate that either arrested or developed into blastocysts. To do this, we sequenced a biopsied blastomere and tracked the developmental potential of the remaining cells. Aneuploid embryos inferred by CNVs from DNA- and RNA-library data tended to lose their developmental potency. Analysis of distinct genomic regions of DNA methylation and chromatin accessibility revealed that enrichment of gene function and signaling pathways, such as the MAPK signaling pathway, was altered in arrested euploid eight-cell embryos compared with blastocyst-developed euploid eight-cell embryos. Moreover, the RNA expression and chromatin accessibility of embryonic genome activation-associated genes were lower in arrested euploid embryos than in blastocyst-developed embryos. Taken together, our results indicate that the developmental block of eight-cell embryos can be caused by multiple molecular layers, including CNVs, abnormality of DNA methylation and chromatin accessibility, and insufficient expression of embryonic genome activation-associated genes. Our integrated and comprehensive data set provides a valuable resource to further dissect the exact mechanisms underlying the arrest of bovine eight-cell embryos in vitro. Summary Sentence Single-cell biopsy and omics technology reveal that the arrest of bovine eight-cell embryos in vitro involves multi-faceted challenges, including CNVs, abnormal DNA methylation and chromatin accessibility, and insufficient expression of EGA genes. Graphical Abstract https://tidbitapp.io/tidbits/dissecting-the-molecular-features-of-bovine-arrested-eight-cell-embryos-using-single-cell-multi-omics-sequencing-9ea06d4e-2288-4849-9969-4eb6d13e80cf