Systematic differences in protein stability underlie species-specific developmental tempo

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Contributors

Abstract

Human embryonic development proceeds more slowly than in mice. The segmentation clock offers a tractable model for studying species-specific developmental tempo, as its oscillation period in human induced presomitic mesoderm (iPSM) cells is approximately twice that of mouse. While the core clock gene HES7 exhibits slower protein degradation in human cells, it remains unclear whether such cross-species differences in protein stability reflect a general principle. Here, we perform a dynamic stable isotope labeling of amino acids in cell culture (SILAC)-based proteomic analysis of ∼5,000 proteins in human and mouse iPSM, and we uncover a broad trend of slower protein degradation in human cells, regardless of subcellular localization or degradation pathways. Moreover, inhibition of glycolysis in mouse iPSM partially phenocopies the human protein stability profile, and modulation of protein stability alters the tempo of both the segmentation clock and cellular differentiation. Our findings establish protein stability, with systematic differences across species, as a key mediator linking metabolism to developmental tempo.

Details

Original languageEnglish
Pages (from-to)1855-1866.e7
JournalDevelopmental cell
Volume61
Issue number9
Early online date13 Aug 2026
Publication statusPublished - 9 Sept 2026
Peer-reviewedYes

External IDs

PubMed 42594862
Mendeley f166f00d-c963-33ed-8109-aa967dfec743

Keywords

Keywords

  • allochrony, cross-species comparison, developmental tempo, metabolism, protein stability, segmentation clock, SILAC proteomics