Comprehensive secretome profiling and CRISPR screen identifies SFRP1 as a key inhibitor of epidermal progenitor proliferation.

ABSTRACT: Secreted proteins are crucial for the structure and functions of the human epidermis, but the full repertoire of the keratinocyte secretome has not been experimentally defined. In this study, we performed mass spectrometry on conditioned media from primary human keratinocytes, identifying 406 proteins with diverse roles in adhesion, migration, proliferation, proteolysis, signal transduction, and innate immunity. To leverage this new dataset, we developed a novel colony formation assay-based CRISPR screen to investigate the functions of uncharacterized secreted proteins on epidermal stem cells. The screen identified six candidate proteins that promoted proliferation of epidermal progenitors and two proteins that inhibited it. Secreted frizzled-related protein-1 (SFRP1) was the most potent i

SUBMITTER: Cheng B 

PROVIDER: S-EPMC12049499 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature