Single-cell analyses unravel cell type–specific responses to a vitamin D analog in prostatic precancerous lesions
Mohamed A. Abu el Maaty, Élise Grelet, Céline Keime, Anna‐Isavella Rerra, Justine Gantzer, C. Emprou, Julie Terzic, Régis Lutzing, Jean‐Marc Bornert, Gilles LAVERNY, Daniel METZGER
Abstract
mice harboring prostatic intraepithelial neoplasia (PIN) with Gemini-72, a vitamin D analog with reported anticancer activities. We show that this analog induces apoptosis in senescent PINs, normalizes extracellular matrix remodeling by stromal fibroblasts, and reduces the prostatic infiltration of immunosuppressive myeloid-derived suppressor cells. Moreover, single-cell RNA-sequencing analysis demonstrates that while a subset of luminal cells expressing Krt8, Krt4, and Tacstd2 (termed luminal-C cells) is lost by such a treatment, antiapoptotic pathways are induced in persistent luminal-C cells. Therefore, our findings delineate the distinct responses of PINs and the microenvironment to Gemini-72, and shed light on mechanisms that limit treatment's efficacy.