ArticleCell death & disease2025
Comprehensive secretome profiling and CRISPR screen identifies SFRP1 as a key inhibitor of epidermal progenitor proliferation.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- AI-guided CRISPR screening reveals therapeutic targets in psoriasis.Nature communications · 2026Article
- The Presence of SFRP1 Reduces the High Risk of Metastasis in RANKL-Expressing Canine Mammary Cancers.Animals : an open access journal from MDPI · 2026Article
- Genetic Engineering of Human Keratinocytes Using CRISPR/Cas9 Ribonucleoprotein Complexes or Modified Cas9-Encoding mRNAs.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Multidimensional Regulatory Mechanisms and Targeted Therapeutic Strategies for Inhibited Keratinocyte Proliferation in Diabetic Wounds.Drug design, development and therapy · 2026Review
- Article
- The mechanism of secreted frizzled-related protein 1 in alleviating cardiomyocyte injury and heart failure.Frontiers in cardiovascular medicine · 2025Review
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Authors and funding
6 authors.
Funding
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 inhibitor. We discovered that SFRP1 restrained clonogenic keratinocyte proliferation by inhibiting Wnt signaling as well as blocking ectopic expression of leukemia inhibitory factor (LIF). Collectively, our study expands our knowledge of the keratinocyte secretome, establishes a novel CRISPR screen to assess the function of non-cell autonomous factors, and highlights SFRP1's role in regulating epidermal balance.
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Registered trials
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