南方医科大学Lin Li和广州医科大学第三附属医院Lei Li共同合作，近期取得重要工作进展。他们通过研究人类着床前胚胎的单细胞多组学，分析识别胚胎停止期间的细胞骨骼缺陷。相关研究成果2024年1月18日在线发表于《自然—细胞生物学》杂志上。

据介绍，人类体外受精胚胎的发育能力较低，胚胎停滞的机制尚不清楚。

研究人员使用单细胞多组学测序方法，同时分析了由于不明原因导致的人类胚胎停滞中转录组、染色质可及性和DNA甲基组的变化。停滞的胚胎表现出转录组紊乱，包括微管细胞骨架扭曲、基因组不稳定性增加和糖酵解受损，这些都与多种表观遗传重编程缺陷有关。研究人员确认了Aurora 一种激酶（AURKA）抑制作为胚胎停滞的原因。

从机制上讲，通过AURKA抑制诱导的停滞胚胎在转录组、DNA甲基组、染色质可及性和H3K4me3修饰方面类似于自然胚胎停滞的重编程异常。停滞胚胎中合子基因组的有丝分裂独立序列激活表明，YY1有助于人类主要合子基因组的激活。

总之，这一研究解码了人类胚胎停滞的重编程异常和机制，以及合子基因组激活的关键调节因子。

附：英文原文

Title: Single-cell multi-omics profiling of human preimplantation embryos identifies cytoskeletal defects during embryonic arrest

Author: Wang, Teng, Peng, Junhua, Fan, Jiaqi, Tang, Ni, Hua, Rui, Zhou, Xueliang, Wang, Zhihao, Wang, Longfei, Bai, Yanling, Quan, Xiaowan, Wang, Zimeng, Zhang, Li, Luo, Chen, Zhang, Weiqing, Kang, Xiangjin, Liu, Jianqiao, Li, Lei, Li, Lin

Issue&Volume: 2024-01-18

Abstract: Human in vitro fertilized embryos exhibit low developmental capabilities, and the mechanisms that underlie embryonic arrest remain unclear. Here using a single-cell multi-omics sequencing approach, we simultaneously analysed alterations in the transcriptome, chromatin accessibility and the DNA methylome in human embryonic arrest due to unexplained reasons. Arrested embryos displayed transcriptome disorders, including a distorted microtubule cytoskeleton, increased genomic instability and impaired glycolysis, which were coordinated with multiple epigenetic reprogramming defects. We identified AuroraA kinase (AURKA) repression as a cause of embryonic arrest. Mechanistically, arrested embryos induced through AURKA inhibition resembled the reprogramming abnormalities of natural embryonic arrest in terms of the transcriptome, the DNA methylome, chromatin accessibility and H3K4me3 modifications. Mitosis-independent sequential activation of the zygotic genome in arrested embryos showed that YY1 contributed to human major zygotic genome activation. Collectively, our study decodes the reprogramming abnormalities and mechanisms of human embryonic arrest and the key regulators of zygotic genome activation.

DOI: 10.1038/s41556-023-01328-0

Source: https://www.nature.com/articles/s41556-023-01328-0