Systematic differences in protein stability underlie species-specific developmental tempo

Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung

Beitragende

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

OriginalspracheEnglisch
Seiten (von - bis)1855-1866.e7
FachzeitschriftDevelopmental cell
Jahrgang61
Ausgabenummer9
Frühes Online-Datum13 Aug. 2026
PublikationsstatusVeröffentlicht - 9 Sept. 2026
Peer-Review-StatusJa

Externe IDs

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

Schlagworte

ASJC Scopus Sachgebiete

  • Molekularbiologie - allochrony, cross-species comparison, developmental tempo, metabolism, protein stability, segmentation clock, SILAC proteomics
  • Allgemeine Biochemie, Genetik und Molekularbiologie - allochrony, cross-species comparison, developmental tempo, metabolism, protein stability, segmentation clock, SILAC proteomics
  • Entwicklungsbiologie - allochrony, cross-species comparison, developmental tempo, metabolism, protein stability, segmentation clock, SILAC proteomics
  • Zellbiologie - allochrony, cross-species comparison, developmental tempo, metabolism, protein stability, segmentation clock, SILAC proteomics

Schlagwörter

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