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Single cell analysis for oocytes and early embryos

ABSTRACT: While non-mammalian embryos often rely on spatial pre-patterning, for decades it was believed that blastomeres of mouse and human embryos were developmentally equivalent. However, emerging evidence suggests early mouse and human blastomeres differ in developmental potential. Here, using multiplexed and label-free single-cell proteomics, we identify over three hundred asymmetrically abundant proteins - many involved in protein degradation and transport - that divide mouse 2-cell stage blastomeres into two distinct clusters, which we term alpha and beta. These asymmetries intensify at the 4-cell stage and are detectable as early as the zygote. Fertilisation acts as a trigger for this breaking of symmetry and sperm entry point correlates with the gradient of proteome asymmetry. Perturbation of beta-enriched proteins (Gps1, Nedd8) alters lineage segregation. Embryos derived from beta blastomeres have more epiblast cells, while alpha blastomeres are associated with a lower developmental potential. Human 2-cell embryos show similar clustering and enrichment patterns, supporting conservation of this early asymmetry. Our findings reveal a previously unrecognized proteomic pre-patterning triggered by fertilisation in mammalian embryos, with implications for understanding totipotency and early lineage bias.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (ncbitaxon:9606) Mus Musculus (ncbitaxon:10090)

SUBMITTER: Tsui-Fen Chou

PROVIDER: MSV000098778 | MassIVE | Sun Aug 10 21:35:00 BST 2025

REPOSITORIES: MassIVE

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Single cell analysis for oocytes and early embryos

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