中国科学院脑智卓越中心刘真等研究人员合作发现，比较蛋白质组学分析揭示人类胚胎着床前发育及其失败的机制。相关论文于2025年1月23日在线发表在《细胞》杂志上。

研究人员应用了全面的超灵敏蛋白质组学技术，来测量卵母细胞和早期胚胎的蛋白质组特征，并在人类中鉴定了近8000种蛋白质，在小鼠中鉴定了超过6,300种蛋白质。研究人员观察到两个物种在受精卵基因组激活（ZGA）前后，存在明显的蛋白质组动态差异。与翻译组学数据的整合分析揭示了，翻译激活与蛋白质积累之间的广泛分歧。

多组学分析表明，ZGA转录本通常有助于囊胚中的蛋白质积累。通过小鼠胚胎，研究人员鉴定了若干对早期发育至关重要的转录调控因子，从而将ZGA与首次谱系分化联系起来。此外，来自100多对患者夫妇的低质量胚胎的单胚胎蛋白质组学分析，提供了关于胚胎着床前发育失败的见解。

该研究可能有助于重塑哺乳动物胚胎着床前发育的框架，并为解决人类不孕症提供新的思路。

据悉，在蛋白质组学层面，理解哺乳动物尤其是人类的胚胎着床前发育仍然有限。

附：英文原文

Title: Comparative proteomic landscapes elucidate human preimplantation development and failure

Author: Wencheng Zhu, Juan Meng, Yan Li, Lei Gu, Wenjun Liu, Ziyi Li, Yi Shen, Xiaoyu Shen, Zihong Wang, Yonggen Wu, Guiquan Wang, Junfeng Zhang, Huiping Zhang, Haiyan Yang, Xi Dong, Hui Wang, Xuefeng Huang, Yidi Sun, Chen Li, Liangshan Mu, Zhen Liu

Issue&Volume: 2025-01-23

Abstract: Understanding mammalian preimplantation development, particularly in humans, at the proteomic level remains limited. Here, we applied our comprehensive solution of ultrasensitive proteomic technology to measure the proteomic profiles of oocytes and early embryos and identified nearly 8,000 proteins in humans and over 6,300 proteins in mice. We observed distinct proteomic dynamics before and around zygotic genome activation (ZGA) between the two species. Integrative analysis with translatomic data revealed extensive divergence between translation activation and protein accumulation. Multi-omic analysis indicated that ZGA transcripts often contribute to protein accumulation in blastocysts. Using mouse embryos, we identified several transcriptional regulators critical for early development, thereby linking ZGA to the first lineage specification. Furthermore, single-embryo proteomics of poor-quality embryos from over 100 patient couples provided insights into preimplantation development failure. Our study may contribute to reshaping the framework of mammalian preimplantation development and opening avenues for addressing human infertility.

DOI: 10.1016/j.cell.2024.12.028

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01470-3