2025-04-23 コペンハーゲン大学(UCPH)
<関連情報>
- https://news.ku.dk/all_news/2025/04/new-research-reveals-how-cancer-drugs-impact-cells-at-the-molecular-level/
- https://www.cell.com/cell/fulltext/S0092-8674(25)00275-2
単一細胞におけるタンパク質代謝動態のグローバル解析 Global analysis of protein turnover dynamics in single cells
Pierre Sabatier ∙ Maico Lechner ∙ Ulises H. Guzmán ∙ … ∙ Karl-Henrik Grinnemo ∙ Zilu Ye ∙ Jesper V. Olsen
Cell Published:March 31, 2025
DOI:https://doi.org/10.1016/j.cell.2025.03.002
Graphical abstract
Highlights
- SC-pSILAC enables protein turnover and abundance measurements in single cells
- SC-pSILAC highlights treatment-related effects of protein-turnover-altering drugs
- Protein turnover underscores functional differences during stem cell differentiation
- Histone turnover distinguishes dividing from slow/non-dividing cells
Summary
Single-cell proteomics (SCPs) has advanced significantly, yet it remains largely unidimensional, focusing primarily on protein abundances. In this study, we employed a pulsed stable isotope labeling by amino acids in cell culture (pSILAC) approach to simultaneously analyze protein abundance and turnover in single cells (SC-pSILAC). Using a state-of-the-art SCP workflow, we demonstrated that two SILAC labels are detectable from ∼4,000 proteins in single HeLa cells recapitulating known biology. We performed a large-scale time-series SC-pSILAC analysis of undirected differentiation of human induced pluripotent stem cells (iPSCs) encompassing 6 sampling times over 2 months and analyzed >1,000 cells. Protein turnover dynamics highlighted differentiation-specific co-regulation of protein complexes with core histone turnover, discriminating dividing and non-dividing cells. Lastly, correlating cell diameter with the abundance of individual proteins showed that histones and some cell-cycle proteins do not scale with cell size. The SC-pSILAC method provides a multidimensional view of protein dynamics in single-cell biology.
