A Single-cell Atlas of Human Prostate Spatially Resolved Using Spatial Transcriptomics

The prostate is an organ with significant spatial heterogeneity. In an effort to elucidate its complex structure and cellular composition, we constructed a comprehensive single-cell atlas of the adult human prostate. Our high-resolution mapping identified 253,381 single cells and 34,876 nuclei, which were categorized into 126 unique subpopulations. This work has revealed not only various novel cell types in the human prostate but also their spatial localization. Importantly, we discovered four distinct acini, two of which were tightly associated with ETS-fusion-negative prostate cancer. Based on integration of spatial, single-cell, and bulk-seq analyses, we propose that two specific luminal cell types could serve as the common origins of prostate cancer. We also found evidence suggesting that zone-specific fibroblasts may contribute to the observed heterogeneity of luminal cells. This atlas will serve as a valuable reference for studying prostate biology and diseases such as prostate cancer.

前列腺是一种具有显著空间异质性的器官。为阐明其复杂的组织结构与细胞组成，我们构建了成人前列腺的全面单细胞图谱。本次高分辨率图谱绘制共鉴定出253381个单细胞与34876个细胞核，并将其划分为126个独特的细胞亚群。本研究不仅揭示了人类前列腺中多种新型细胞类型，还明确了其空间定位。尤为重要的是，我们发现了四种不同的腺泡，其中两种与ETS融合阴性（ETS-fusion-negative）前列腺癌紧密相关。通过整合空间、单细胞与bulk-seq分析，我们提出两种特定的腔上皮细胞类型可作为前列腺癌的共同起源。此外，我们还发现证据表明，区域特异性成纤维细胞可能是导致腔上皮细胞异质性的关键因素之一。本图谱将为前列腺生物学及前列腺癌等相关疾病的研究提供极具价值的参考依据。