Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer
| Autor: | Noel W. Clarke, Esther Baena, Guo-Cheng Yuan, Ivana Steiner, Douglas E. Linn, Garry Ashton, Hubert Pakula, Isabel Peset, Roderick T. Bronson, Zhe Li, Stuart H. Orkin, Adnan Ali, Guoji Guo, João D. Barros-Silva, Michael D Brown |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Carcinogenesis Mice Transgenic Biology GPI-Linked Proteins tumor-initiating cells General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Prostate cancer Mice LY6D Castration Resistance Single-cell analysis luminal progenitor Prostate Gene expression medicine Biomarkers Tumor PTEN Animals Humans Regeneration castration-resistant prostate cancer Cell Lineage Progenitor cell Gene lcsh:QH301-705.5 Manchester Cancer Research Centre ResearchInstitutes_Networks_Beacons/mcrc Epithelial Cells medicine.disease Mice Inbred C57BL Organoids intrinsic resistance Prostatic Neoplasms Castration-Resistant 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Cancer research biology.protein Disease Progression Neoplastic Stem Cells Single-Cell Analysis Cell Adhesion Molecules |
| Zdroj: | Barros-Silva, J D, Linn, D E, Steiner, I, Guo, G, Ali, A, Pakula, H, Ashton, G, Peset, I, Brown, M, Clarke, N W, Bronson, R T, Yuan, G-C, Orkin, S H, Li, Z & Baena, E 2018, ' Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer ', Cell Reports, vol. 25, no. 12, pp. 3504-3518.e6 . https://doi.org/10.1016/j.celrep.2018.11.069 Cell Reports Cell Reports, Vol 25, Iss 12, Pp 3504-3518.e6 (2018) |
| Popis: | Summary The exact identity of castrate-resistant (CR) cells and their relation to CR prostate cancer (CRPC) is unresolved. We use single-cell gene profiling to analyze the molecular heterogeneity in basal and luminal compartments. Within the luminal compartment, we identify a subset of cells intrinsically resistant to castration with a bi-lineage gene expression pattern. We discover LY6D as a marker of CR prostate progenitors with multipotent differentiation and enriched organoid-forming capacity. Lineage tracing further reveals that LY6D+ CR luminal cells can produce LY6D− luminal cells. In contrast, in luminal cells lacking PTEN, LY6D+ cells predominantly give rise to LY6D+ tumor cells, contributing to high-grade PIN lesions. Gene expression analyses in patients’ biopsies indicate that LY6D expression correlates with early disease progression, including progression to CRPC. Our studies thus identify a subpopulation of luminal progenitors characterized by LY6D expression and intrinsic castration resistance. LY6D may serve as a prognostic maker for advanced prostate cancer. Graphical Abstract Highlights • Single-cell analysis identifies a highly heterogeneous luminal compartment • LY6D marks luminal cells that are resistant to castration with bi-lineage capacity • LY6D correlates with prostate cancer development from luminal lineage • LY6D expression in human prostate cancer correlates with early disease progression To address the identity of castration-resistant prostate cells in vivo, Barros-Silva et al. coupled single-cell analysis with organoid culture and in situ lineage tracing. They identify LY6D as a progenitor marker that liaises intrinsically castration-resistant luminal cells and castration-resistant prostate tumor growth. |
| Databáze: | OpenAIRE |
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