期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 15, 页码 -出版社
MDPI
DOI: 10.3390/ijms22158109
关键词
prostate cancer; stem cells; keratin; RNA-seq; single cell; lineage hierarchy; differentiation
资金
- NIH/NIEHS [RO1ES022071]
- NCI [RO1CA172220-01]
- DoD [PC180408]
- Michael Reese Research and Education Foundation Translational Research Grant Award
This study characterized the epithelial cell lineage hierarchy in prostaspheres using single-cell RNA-seq analysis and keratin profiling. It identified distinct clusters of stem cells and progenitor cells based on marker expression and gene enrichment pathways. Understanding the keratin profiles in human prostate stem cell lineage hierarchy and cancer stem-like cells may aid in the identification and targeted therapy of prostate cancer stem-like cells.
Single prostate stem cells can generate stem and progenitor cells to form prostaspheres in 3D culture. Using a prostasphere-based label retention assay, we recently identified keratin 13 (KRT13)-enriched prostate stem cells at single-cell resolution, distinguishing them from daughter progenitors. Herein, we characterized the epithelial cell lineage hierarchy in prostaspheres using single-cell RNA-seq analysis. Keratin profiling revealed three clusters of label-retaining prostate stem cells; cluster I represents quiescent stem cells (PSCA, CD36, SPINK1, and KRT13/23/80/78/4 enriched), while clusters II and III represent active stem and bipotent progenitor cells (KRT16/17/6 enriched). Gene set enrichment analysis revealed enrichment of stem and cancer-related pathways in cluster I. In non-label-retaining daughter progenitor cells, three clusters were identified; cluster IV represents basal progenitors (KRT5/14/6/16 enriched), while clusters V and VI represent early and late-stage luminal progenitors, respectively (KRT8/18/10 enriched). Furthermore, MetaCore analysis showed enrichment of the cytoskeleton remodeling-keratin filaments pathway in cancer stem-like cells from human prostate cancer specimens. Along with common keratins (KRT13/23/80/78/4) in normal stem cells, unique keratins (KRT10/19/6C/16) were enriched in cancer stem-like cells. Clarification of these keratin profiles in human prostate stem cell lineage hierarchy and cancer stem-like cells can facilitate the identification and therapeutic targeting of prostate cancer stem-like cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据