Year: 2026
Type: article
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.
Source: Developmental Cell
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Alexander von Humboldt-Stiftung, Boehringer Ingelheim, European Molecular Biology Laboratory, Paul G. Allen Frontiers Group, European Commission, Boehringer Ingelheim Fonds, Deutsche Forschungsgemeinschaft, Ministry of Education, Culture, Sports, Science and Technology, Bundesministerium für Bildung und Forschung, Technische Universität Dresden, European Research Council, Japan Science and Technology Agency, RIKEN, Precursory Research for Embryonic Science and Technology, H2020 Marie Skłodowska-Curie Actions, HORIZON EUROPE Marie Sklodowska-Curie Actions
OpenAlex ID: W7202343776