Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

嗅觉调节蛋白4（Olfm 4）在正常小鼠前列腺中表达。然而，小鼠前列腺中的Olfm 4+细胞尚未得到很好的表征。在这项研究中，我们产生了一个Olfm 4 eGFP报告小鼠系与C57 BL/6小鼠，并研究了Olfm 4/eGFP表达细胞在出生后发育过程中从P1，P7，P14，P20，P42，P56到成年雄性小鼠前列腺和尿道管的分布。我们观察到Olfm 4/eGFP表达在泌尿生殖道和前列腺上皮细胞在出生后早期的发展，持续到成年期的尿道管和前前列腺（AP）上皮。结果发现，在成年小鼠AP上皮中，Olfm 4+细胞为E-cadherin+/CD 44 +/Foxa 1+，部分细胞亚群为Ck 8 +/Ck 5 +/Sca-1-/Ck 4-/Syn-。从成年Olfm 4 eGFP小鼠前列腺分离的表达Olfm 4/eGFP的细胞的单细胞制备物的功能研究表明，Olfm 4+细胞可以在培养物中生长并形成集落、球体或类器官。在成年小鼠尿道（GSE 145865）中使用单细胞RNA测序Meta数据的Olfm 4+细胞的生物信息学分析鉴定了与细胞和组织迁移和发育相关的基因的上调，以及异生物质代谢信号传导途径的上调。总之，Olfm 4 eGFP小鼠是进一步研究Olfm 4的生物学功能的新模型，Olfm 4+细胞可能对支持小鼠前列腺和尿道管上皮的发育和稳态的细胞过程做出重要贡献。

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.