Keratin Profiling by Single-Cell RNA-Sequencing Identifies Human Prostate Stem Cell Lineage Hierarchy and Cancer Stem-Like Cells.
Keratin Profiling by Single-Cell RNA-Sequencing Identifies Human Prostate Stem Cell Lineage Hierarchy and Cancer Stem-Like Cells.
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DOI：
10.3390/ijms22158109
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发表时间：
2021-07-28
影响因子：
5.6
通讯作者：
Prins GS
中科院分区：
文献类型：
--
作者：
Hu WY;Hu DP;Xie L;Nonn L;Lu R;Abern M;Shioda T;Prins GS
单个前列腺干细胞在三维培养中可以产生干细胞和祖细胞形成前列腺球。利用基于前列腺球的标记保留试验，我们最近在单细胞分辨率下鉴定出富含角蛋白13 （KRT13）的前列腺干细胞，并将其与子祖细胞区分开来。在此，我们使用单细胞RNA-seq分析表征了前列腺球体上皮细胞的谱系结构。角蛋白谱显示了三组保留标签的前列腺干细胞；集群I代表静止干细胞（PSCA、CD36、SPINK1和KRT13/23/80/78/4富集），集群II和III代表活跃的干细胞和双能祖细胞（KRT16/17/6富集）。基因集富集分析显示，在集群i中富集了干细胞和癌症相关通路。在非保留标记的子祖细胞中，鉴定出三个集群；集群IV代表基底祖细胞（KRT5/14/6/16富集），集群V和集群VI分别代表早期和晚期管腔祖细胞（KRT8/18/10富集）。此外，MetaCore分析显示，来自人类前列腺癌标本的癌干细胞样细胞中富集了“细胞骨架重塑-角蛋白丝”通路。除了在正常干细胞中常见的角蛋白（KRT13/23/80/78/4）外，独特的角蛋白（KRT10/19/6C/16）在癌症干细胞样细胞中富集。澄清这些角蛋白在人类前列腺干细胞谱系结构和癌症干细胞样细胞中的分布，可以促进前列腺癌干细胞样细胞的鉴定和治疗靶向。
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.