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Updated: Aug 15, 2026

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Published on: January 28, 2015
Systematic differences in protein stability underlie species-specific developmental tempo
Mitsuhiro Matsuda1, Henrik M Hammarén2, Jorge Lázaro3
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.
Human cells exhibit slower protein degradation than mouse cells, impacting developmental tempo. This discovery links cellular metabolism to species-specific embryonic development rates.
Area of Science:
- Developmental Biology
- Proteomics
- Cellular Metabolism
Background:
- Human embryonic development is slower than murine development.
- The segmentation clock, with its species-specific oscillation periods, serves as a model for developmental tempo.
- Human induced presomitic mesoderm (iPSM) cells show a segmentation clock period twice that of mouse iPSM cells, with HES7 protein exhibiting slower degradation in humans.
Purpose of the Study:
- To investigate whether slower protein degradation is a general principle across species.
- To explore the link between protein stability, metabolism, and developmental tempo.
Main Methods:
- Dynamic stable isotope labeling of amino acids in cell culture (SILAC)-based proteomic analysis of approximately 5,000 proteins in human and mouse iPSM cells.
- Inhibition of glycolysis in mouse iPSM cells.
- Modulation of protein stability.
Main Results:
- A broad trend of slower protein degradation was observed in human iPSM cells compared to mouse iPSM cells, irrespective of subcellular localization or degradation pathway.
- Inhibition of glycolysis in mouse iPSM cells partially mimicked the human protein stability profile.
- Altering protein stability affected the tempo of both the segmentation clock and cellular differentiation.
Conclusions:
- Systematic differences in protein stability exist between human and mouse cells.
- Protein stability acts as a crucial mediator connecting cellular metabolism to developmental tempo.
- These findings provide insights into the molecular mechanisms underlying species-specific developmental rates.
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