Prostate Sphere-forming Stem Cells Are Derived from the P63-expressing Basal Compartment
Prostate Sphere-forming Stem Cells Are Derived from the P63-expressing Basal Compartment
复制标题
前列腺球形成干细胞源自表达 P63 的基底室
DOI：
10.1074/jbc.m115.661033
复制
发表时间：
2015-07-17
影响因子：
4.8
通讯作者：
Wang, Fen
中科院分区：
文献类型：
--
作者：
Huang, Yanqing;Hamana, Tomoaki;Wang, Fen
前列腺干细胞（P-SC）能够产生前列腺上皮细胞的所有三个谱系，包括基底细胞、管腔细胞和神经内分泌细胞。已经使用多种方法来鉴定成人前列腺中的P-SC。这些包括单个上皮细胞与泌尿生殖间充质细胞的体内肾包膜植入、体外前列腺球和类器官培养、以及去势抵抗性Nkx 3.1表达（卡恩）的谱系追踪，以及细胞类型特异性标志物的表达。类器官培养和卡恩示踪均显示在腔室中存在P-SC。虽然前列腺球细胞主要表达基底细胞特异性细胞角蛋白和P63，但P-SC层次中前列腺球形成细胞的谱系仍有待确定。使用P63（CreERT 2）的谱系追踪，我们在这里表明，形成球体的P-SC是P63表达细胞，并驻留在基底室。因此，我们将它们命名为基础P-SC（P-bSC）。P-bSC能够分化为AR（+）和CK 18（+）类器官细胞，但类器官细胞不能形成球体。我们还报告说，前列腺含有静止干细胞。因此，结果显示P-bSC代表在整个前列腺组织干细胞层级中早期的干细胞。了解这两种类型的P-SC对前列腺发育和前列腺癌干细胞的贡献以及如何操纵它们可能为控制前列腺癌进展和复发开辟新的途径。
Prostate stem cells (P-SCs) are capable of giving rise to all three lineages of prostate epithelial cells, including basal, luminal, and neuroendocrine cells. Multiple methods have been used to identify P-SCs in adult prostates. These include in vivo renal capsule implantation of a single epithelial cell with urogenital mesenchymal cells, in vitro prostasphere and organoid cultures, and lineage tracing with castration-resistant Nkx3.1 expression (CARN), in conjunction with expression of cell type-specific markers. Both organoid culture and CARN tracing show the existence of P-SCs in the luminal compartment. Although prostasphere cells predominantly express basal cell-specific cytokeratin and P63, the lineage of prostasphere-forming cells in the P-SC hierarchy remains to be determined. Using lineage tracing with P63(CreERT2), we show here that the sphere-forming P-SCs are P63-expressing cells and reside in the basal compartment. Therefore we designate them as basal P-SCs (P-bSCs). P-bSCs are capable of differentiating into AR(+) and CK18(+) organoid cells, but organoid cells cannot form spheres. We also report that prostaspheres contain quiescent stem cells. Therefore, the results show that P-bSCs represent stem cells that are early in the hierarchy of overall prostate tissue stem cells. Understanding the contribution of the two types of P-SCs to prostate development and prostate cancer stem cells and how to manipulate them may open new avenues for control of prostate cancer progression and relapse.