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膀胱尤因肉瘤的单细胞RNA测序和空间转录组学

Single-cell RNA sequencing and spatial transcriptomics of bladder Ewing sarcoma.

作者信息

Mao Weipu, Xu Kangjie, Wang Keyi, Zhang Houliang, Ji Jie, Geng Jiang, Sun Si, Gu Chaoming, Bhattacharya Atrayee, Fang Cheng, Tao Tao, Chen Ming, Wu Jianping, Chen Shuqiu, Sun Chao, Xu Bin

机构信息

Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, China.

Central Laboratory Department, Binhai County People's Hospital, Yancheng 224000, China.

出版信息

iScience. 2024 Sep 11;27(10):110921. doi: 10.1016/j.isci.2024.110921. eCollection 2024 Oct 18.

DOI:10.1016/j.isci.2024.110921
PMID:39386756
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11462044/
Abstract

Bladder Ewing sarcoma/primitive neuroectodermal tumor (bladder ES/PNET) is a rare and highly malignant tumor associated with a poor prognosis, yet its underlying mechanisms remain poorly understood. Here, we employed a combination of single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and functional analyses to delve into the pathogenesis of bladder ES/PNET. The investigation revealed the presence of specialized types of epithelial cells (referred to as bladder ES-Epi) and mast cells (referred to as bladder ES-Mast) within bladder ES/PNET in comparison to urothelial carcinoma. Notably, TNFRSF12A exhibited significant upregulation in bladder ES/PNET. Furthermore, mast cells possessed the ability to activate epithelial cells through the TNFSF12-TNFRSF12A ligand-receptor signaling pattern. In addition, Enavatuzumab can significantly inhibit the migratory ability of the Ewing sarcoma cell line RD-ES. This groundbreaking study provides unprecedented mechanistic insights into the progression of bladder ES/PNET and introduces a potential therapeutic avenue for treating this challenging malignancy.

摘要

膀胱尤因肉瘤/原始神经外胚层肿瘤（膀胱ES/PNET）是一种罕见的高恶性肿瘤，预后较差，但其潜在机制仍知之甚少。在此，我们采用单细胞RNA测序（scRNA-seq）、空间转录组学（ST）和功能分析相结合的方法，深入探究膀胱ES/PNET的发病机制。研究发现，与尿路上皮癌相比，膀胱ES/PNET中存在特殊类型的上皮细胞（称为膀胱ES-Epi）和肥大细胞（称为膀胱ES-Mast）。值得注意的是，TNFRSF12A在膀胱ES/PNET中显著上调。此外，肥大细胞能够通过TNFSF12-TNFRSF12A配体-受体信号模式激活上皮细胞。此外，Enavatuzumab可显著抑制尤因肉瘤细胞系RD-ES的迁移能力。这项开创性的研究为膀胱ES/PNET的进展提供了前所未有的机制见解，并为治疗这种具有挑战性的恶性肿瘤引入了一条潜在的治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/fb9422064f80/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/901fe070e06d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/bf777bbfb87e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/a5566045e565/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/1cc05f28af2a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/19f08dc8e377/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/41bd439deb99/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/fb9422064f80/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/901fe070e06d/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/bf777bbfb87e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/a5566045e565/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/1cc05f28af2a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/19f08dc8e377/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/41bd439deb99/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c24/11462044/fb9422064f80/gr6.jpg

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Self-supervised deep clustering of single-cell RNA-seq data to hierarchically detect rare cell populations.
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Integrated single-cell and spatial transcriptomic profiling reveals higher intratumour heterogeneity and epithelial-fibroblast interactions in recurrent bladder cancer.整合单细胞和空间转录组分析揭示复发性膀胱癌中更高的肿瘤内异质性和上皮-成纤维细胞相互作用。
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