Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer

被引：70

作者：

Barros-Silva, Joao D. ^{[1
,9
]}

Linn, Douglas E. ^{[2
,3
]}

Steiner, Ivana ^{[1
,9
]}

Guo, Guoji ^{[4
,5
]}

Ali, Adnan ^{[1
,9
]}

Pakula, Hubert ^{[2
,3
]}

Ashton, Garry ^{[6
]}

Peset, Isabel ^{[7
]}

Brown, Michael ^{[8
,9
]}

Clarke, Noel W. ^{[8
,9
,10
]}

Bronson, Roderick T. ^{[11
]}

Yuan, Guo-Cheng ^{[12
]}

Orkin, Stuart H. ^{[4
,5
,13
]}

Li, Zhe ^{[2
,3
]}

Baena, Esther ^{[1
,9
]}

机构：

[1] Univ Manchester, Canc Res UK Manchester Inst, Prostate Oncobiol, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England

[2] Harvard Med Sch, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[3] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[4] Harvard Med Sch, Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA

[5] Harvard Med Sch, Harvard Stem Cell Inst, Dana Farber Canc Inst, Boston, MA 02115 USA

[6] Univ Manchester, Canc Res UK Manchester Inst, Histol Unit, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England

[7] Univ Manchester, Canc Res UK Manchester Inst, Imaging Unit, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England

[8] Univ Manchester, Manchester Canc Res Ctr, Fac Biol Med & Hlth, Genitourinary Canc Res,Div Canc Sci,Sch Med Sci, Wilmslow Rd, Manchester M20 4GJ, Lancs, England

[9] Univ Manchester, Canc Res UK Manchester Inst, Belfast Manchester Movember Ctr Excellence, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England

[10] Salford Royal Hosp, Christie Hosp, Dept Urol, Dept Surg, Manchester, Lancs, England

[11] Harvard Med Sch, Rodent Histopathol, Boston, MA 02115 USA

[12] Harvard Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[13] Howard Hughes Med Inst, Boston, MA 02115 USA

来源：

CELL REPORTS | 2018年 / 25卷 / 12期

关键词：

EPITHELIAL-CELLS; STEM-CELLS; INCREASED SURVIVAL; CONSENSUS REPORT; MOUSE MODELS; IN-VITRO; ORIGIN; SURFACE; BASAL; ORGANOIDS;

D O I：

10.1016/j.celrep.2018.11.069

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：3504 / +

页数：21

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