Systematic differences in protein stability underlie species-specific developmental tempo
Research output: Contribution to journal › Research article › Contributed › peer-review
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 language | English |
|---|---|
| Pages (from-to) | 1855-1866.e7 |
| Journal | Developmental cell |
| Volume | 61 |
| Issue number | 9 |
| Early online date | 13 Aug 2026 |
| Publication status | Published - 9 Sept 2026 |
| Peer-reviewed | Yes |
External IDs
| PubMed | 42594862 |
|---|---|
| Mendeley | f166f00d-c963-33ed-8109-aa967dfec743 |
Keywords
ASJC Scopus subject areas
Keywords
- allochrony, cross-species comparison, developmental tempo, metabolism, protein stability, segmentation clock, SILAC proteomics