加州理工学院Magdalena Zernicka-Goetz小组近日取得一项新成果。经过不懈努力，他们的研究发现受精触发哺乳动物胚胎早期蛋白质组对称性断裂。2025年12月3日，国际知名学术期刊《细胞》发表了这一成果。
以多重和无标记的单细胞蛋白质组学为主题，该研究团队鉴定了超过300种不对称丰富的蛋白质-许多参与蛋白质降解和运输-将2细胞阶段的母细胞卵裂球分裂成两个不同的细胞，该研究团队称之为α和β。这些蛋白质组不对称早在受精卵阶段就可以检测到，在4细胞阶段加强，并与精子进入位点相关，暗示受精是一个对称性破坏事件。将2细胞阶段的胚胎分成两半表明β卵裂球比α卵裂球具有更大的发育潜力。在人类2细胞胚胎中发现的类似的克隆和蛋白质富集模式表明，这种早期不对称可能是保守的。这些发现揭示了哺乳动物胚胎受精引发的一种以前未被认识到的蛋白质组学预模式，对理解全能性和早期谱系偏见具有重要意义。
研究人员表示，虽然非哺乳动物胚胎通常依赖于空间预模式，但哺乳动物的发育长期以来一直被认为是从等效的卵裂球开始的。然而，新出现的证据挑战了这一点。
附：英文原文
Title: Fertilization triggers early proteomic symmetry breaking in mammalian embryos
Author: Lisa K. Iwamoto-Stohl, Aleksandra A. Petelski, Baiyi Quan, Maciej Meglicki, Audrey Fu, Shoma Nakagawa, Breanna McMahon, Ting-Yu Wang, Saad Khan, Harrison Specht, Gray Huffman, Jason Derks, Sergi Junyent, Bailey A.T. Weatherbee, Antonia Weberling, Carlos W. Gantner, Rachel S. Mandelbaum, Richard J. Paulson, Lisa Lam, Tsui-Fen Chou, Nikolai Slavov, Magdalena Zernicka-Goetz
Issue&Volume: 2025-12-03
Abstract: While non-mammalian embryos often rely on spatial pre-patterning, mammalian development has long been thought to begin with equivalent blastomeres. However, emerging evidence challenges this. Here, using multiplexed and label-free single-cell proteomics, we identify over 300 asymmetrically abundant proteins—many involved in protein degradation and transport—dividing mouse 2-cell-stage blastomeres into two distinct clusters, which we term alpha and beta. These proteomic asymmetries are detectable as early as the zygote stage, intensify by the 4-cell stage, and correlate with the sperm entry site, implicating fertilization as a symmetry-breaking event. Splitting 2-cell-stage embryos into halves reveals that beta blastomeres possess greater developmental potential than alpha blastomeres. Similar clustering and protein enrichment patterns found in human 2-cell embryos suggest this early asymmetry might be conserved. These findings uncover a previously unrecognized proteomic pre-patterning triggered by fertilization in mammalian embryos, with important implications for understanding totipotency and early lineage bias.
DOI: 10.1016/j.cell.2025.11.006
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01255-3