Single-cell analysis identifies LY6D as a marker linking castration-resistant prostate luminal cells to prostate progenitors and cancer
Authors
Barros-Silva, Joao DLinn, D
Steiner, I
Guo, G
Ali, Adnan
Pakula, H
Ashton, Garry
Peset, I
Brown, Michael D
Clarke, Noel W
Bronson, R
Yuan, G
Orkin, S
Li, Z
Baena, Esther
Affiliation
Prostate Oncobiology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, UKIssue Date
2018
Metadata
Show full item recordAbstract
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.Citation
Barros-Silva JD, Linn DE, Steiner I, Guo G, Ali A, Pakula H, et al. Single-cell analysis identifies LY6D as a marker linking castration-resistant prostate luminal cells to prostate progenitors and cancer. Cell Rep. 2018 Dec 18;25(12):3504-18 e6.Journal
Cell ReportsDOI
10.1016/j.celrep.2018.11.069PubMed ID
30566873Additional Links
https://dx.doi.org/10.1016/j.celrep.2018.11.069Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2018.11.069
Scopus Count
Collections
Related articles
- A rare castration-resistant progenitor cell population is highly enriched in Pten-null prostate tumours.
- Authors: Sackmann Sala L, Boutillon F, Menara G, De Goyon-Pélard A, Leprévost M, Codzamanian J, Lister N, Pencik J, Clark A, Cagnard N, Bole-Feysot C, Moriggl R, Risbridger GP, Taylor RA, Kenner L, Guidotti JE, Goffin V
- Issue date: 2017 Sep
- Histone 2B-GFP Label-Retaining Prostate Luminal Cells Possess Progenitor Cell Properties and Are Intrinsically Resistant to Castration.
- Authors: Zhang D, Jeter C, Gong S, Tracz A, Lu Y, Shen J, Tang DG
- Issue date: 2018 Jan 9
- Single luminal epithelial progenitors can generate prostate organoids in culture.
- Authors: Chua CW, Shibata M, Lei M, Toivanen R, Barlow LJ, Bergren SK, Badani KK, McKiernan JM, Benson MC, Hibshoosh H, Shen MM
- Issue date: 2014 Oct
- Bmi1 marks distinct castration-resistant luminal progenitor cells competent for prostate regeneration and tumour initiation.
- Authors: Yoo YA, Roh M, Naseem AF, Lysy B, Desouki MM, Unno K, Abdulkadir SA
- Issue date: 2016 Oct 5
- Conditionally ablated Pten in prostate basal cells promotes basal-to-luminal differentiation and causes invasive prostate cancer in mice.
- Authors: Lu TL, Huang YF, You LR, Chao NC, Su FY, Chang JL, Chen CM
- Issue date: 2013 Mar