Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States of America.
Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States of America.
PLoS One. 2020 Jun 25;15(6):e0233899. doi: 10.1371/journal.pone.0233899. eCollection 2020.
Studies of the normal functions and diseases of the prostate request in vivo models that maintain the tissue architecture and the multiple-cell type compartments of human origin in order to recapitulate reliably the interactions of different cell types. Cell type-specific transcriptomes are critical to reveal the roles of each cell type in the functions and diseases of the prostate. A primary prostate tissue xenograft model was developed using fresh human prostate tissue specimens transplanted onto male mice that were castrated surgically and implanted with a device to maintain circulating testosterone levels comparable to adult human males. Endothelial cells and epithelial cells were isolated from 7 fresh human prostate tissue specimens and from primary tissue xenografts established from 9 fresh human prostate tissue specimens, using antibody-conjugated magnetic beads specific to human CD31 and human EpCAM, respectively. Transcriptomes of endothelial, epithelial and stromal cell fractions were obtained using RNA-Seq. Global and function-specific gene expression profiles were compared in inter-cell type and inter-tissue type manners. Gene expression profiles in the individual cell types isolated from xenografts were similar to those of cells isolated from fresh tissue, demonstrating the value of the primary tissue xenograft model for studies of the inter-relationships between prostatic cell types and the role of such inter-relationships in organ development, disease progression, and response to drug treatments.
为了可靠地再现不同细胞类型的相互作用，研究前列腺的正常功能和疾病需要体内模型来维持组织架构和源自人体的多细胞类型隔室。细胞类型特异性转录组对于揭示每个细胞类型在前列腺功能和疾病中的作用至关重要。使用新鲜的人前列腺组织标本移植到经过手术去势并植入装置以维持循环睾酮水平与成年男性相当的雄性小鼠上，建立了原发性前列腺组织异种移植模型。使用分别针对人 CD31 和人 EpCAM 的抗体偶联磁珠，从 7 个人类新鲜前列腺组织标本和 9 个人类新鲜前列腺组织标本建立的原发性组织异种移植中分离出内皮细胞和上皮细胞。使用 RNA-Seq 获得内皮细胞、上皮细胞和基质细胞部分的转录组。以细胞间和组织间的方式比较了全局和功能特异性基因表达谱。从异种移植物中分离出的单个细胞类型的基因表达谱与从新鲜组织中分离出的细胞的基因表达谱相似，这表明原发性组织异种移植模型对于研究前列腺细胞类型之间的相互关系以及这种相互关系在器官发育、疾病进展和药物治疗反应中的作用具有重要价值。
