2025-12-03 カリフォルニア工科大学(Caltech)
<関連情報>
- https://www.caltech.edu/about/news/the-earliest-stage-of-embryos-show-specialized-asymmetry
- https://www.cell.com/cell/fulltext/S0092-8674(25)01255-3
受精は哺乳類の胚における初期のプロテオーム対称性の破壊を引き起こす Fertilization triggers early proteomic symmetry breaking in mammalian embryos
Lisa K. Iwamoto-Stohl ∙ Aleksandra A. Petelski ∙ Baiyi Quan ∙ … ∙ Tsui-Fen Chou, ∙ Nikolai Slavov ∙ Magdalena Zernicka-Goetz
Cell Published:December 3, 2025
DOI:https://doi.org/10.1016/j.cell.2025.11.006
Graphical abstract
Highlights
- Proteomic asymmetries emerge at the zygote stage and are triggered by fertilization
- 2-cell-stage blastomeres cluster into alpha and beta states with unique profiles
- Beta blastomeres show greater developmental potential than alpha blastomeres
- Early asymmetries are conserved in human embryos
Summary
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.
