Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

olfactomed4 （Olfm4）在正常小鼠前列腺中表达。然而，小鼠前列腺中的Olfm4+细胞尚未被很好地表征。本研究以C57BL/6小鼠为对象，构建了Olfm4/ egfp报告细胞小鼠系，研究了从P1、P7、P14、P20、P42、P56到成年雄性小鼠前列腺和尿道管发育过程中表达Olfm4/ egfp细胞的分布。我们观察到Olfm4/eGFP在出生后早期的泌尿生殖和前列腺上皮细胞中表达，并在尿道管和前列腺前（AP）上皮中持续到成年。我们发现成年小鼠AP上皮中Olfm4+细胞为E-cadherin+/CD44+/Foxa1+，部分亚群为Ck8+/Ck5+/ ca-1-/Ck4-/Syn-。从成年Olfm4eGFP小鼠前列腺中分离的表达Olfm4/ egfp的细胞单细胞制备的功能研究表明，Olfm4+细胞可以生长并形成菌落、球体或类器官。利用单细胞RNA测序元数据对成年小鼠尿道（GSE145865）中的Olfm4+细胞进行生物信息学分析，发现细胞和组织迁移和发育相关基因上调，以及外源代谢信号通路上调。综上所述，Olfm4eGFP小鼠是进一步研究Olfm4生物学功能的新模型，Olfm4+细胞可能在支持小鼠前列腺和尿道管上皮发育和稳态的细胞过程中发挥重要作用。

Olfactomedin4 (Olfm4) is expressed in normal mouse prostate. However, Olfm4+ cells in the murine prostate have not been well characterized. In this study, we generated an Olfm4eGFP reporter mouse line with C57BL/6 mice and investigated the distribution of Olfm4/eGFP-expressing cells during postnatal development from P1, P7, P14, P20, P42, P56 to adult male mouse prostate and urethral tube. We observed Olfm4/eGFP expression in urogenital and prostatic epithelial cells during early postnatal development, which persisted into adulthood in urethral-tube and anterior-prostate (AP) epithelium. We found Olfm4+ cells are E-cadherin+/CD44+/Foxa1+ and some of subpopulation are Ck8+/Ck5+/Sca-1-/Ck4-/Syn- in the adult mouse AP epithelium. Functional studies of single-cell preparations of Olfm4/eGFP-expressing cells isolated from adult Olfm4eGFP mouse prostate demonstrated that Olfm4+ cells can grow and form colonies, spheres, or organoids in culture. Bioinformatic analysis of Olfm4+ cells using single-cell RNA sequencing meta data in adult mouse urethra (GSE145865) identified upregulation of genes related to cell and tissue migration and development, as well as upregulation of xenobiotic metabolism signaling pathways. In conclusion, Olfm4eGFP mouse is a novel model to further study Olfm4's biological functions and Olfm4+ cells may contribute importantly to cellular processes supporting development and homeostasis of the epithelium in murine prostate and urethral tube.