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Peer-reviewedCC BYDevelopmental Cell

Systematic differences in protein stability underlie species-specific developmental tempo

  • Mitsuhiro Matsuda1
  • Henrik M. Hammarén2
  • Jorge Lázaro3
  • Mikhail M. Savitski4
  • Miki Ebisuya5
5 affiliations
  1. 1European Molecular Biology Laboratory, EMBL Barcelona, C/ Dr. Aiguader, 88, PRBB Building, 08003 Barcelona, Spain; Cluster of Excellence Physics of Life, TU Dresden, 01307 Dresden, Germany
  2. 2European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany
  3. 3European Molecular Biology Laboratory, EMBL Barcelona, C/ Dr. Aiguader, 88, PRBB Building, 08003 Barcelona, Spain; Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany
  4. 4European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany. Electronic address: [email protected]
  5. 5European Molecular Biology Laboratory, EMBL Barcelona, C/ Dr. Aiguader, 88, PRBB Building, 08003 Barcelona, Spain; Cluster of Excellence Physics of Life, TU Dresden, 01307 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany. Electronic address: [email protected]
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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.

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Cite

BibTeXRIS
BibTeX
@article{matsuda2026systematic,
  title = {{Systematic differences in protein stability underlie species-specific developmental tempo}},
  author = {Mitsuhiro Matsuda and Henrik M. Hammarén and Jorge Lázaro and Mikhail M. Savitski and Miki Ebisuya},
  journal = {Developmental Cell},
  year = {2026},
  month = aug,
  doi = {10.1016/j.devcel.2026.07.012},
  url = {https://doi.org/10.1016/j.devcel.2026.07.012},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Systematic differences in protein stability underlie species-specific developmental tempo
AU  - Mitsuhiro Matsuda
AU  - Henrik M. Hammarén
AU  - Jorge Lázaro
AU  - Mikhail M. Savitski
AU  - Miki Ebisuya
PY  - 2026
DA  - 2026/08/13
JO  - Developmental Cell
DO  - 10.1016/j.devcel.2026.07.012
UR  - https://doi.org/10.1016/j.devcel.2026.07.012
AB  - 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.
SN  - 1534-5807
SN  - 1878-1551
ER  -