Cell-type resolved prenylomics in mouse liver enabled by a low-input proteomics workflow

A low-input prenylomics workflow profiles cell-type-specific prenylomes in mouse liver from 50 ug total protein, identifying 29 hepatocyte and 18 macrophage prenylated proteins after probe administration.

• Why it matters: Prenylation dysregulation is linked to cancer and neurodegenerative diseases, but standard prenylomic workflows need milligram-scale inputs, limiting studies of scarce primary or sorted cell populations.
• What they did: The authors optimized streptavidin enrichment with library-free DIA mass spectrometry, achieving deep prenylomic coverage from 50 ug input (a 20-fold reduction) and validating performance in COS7 cells.
• The result: In COS7 cells, the method identified 91 prenylated protein groups versus 81 with TMT-DDA from 2 mg input, and in mice it enabled cell-type-specific profiling consistent with each cell-type’s biology.