Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection.
Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection.
复制标题
DOI：
10.1186/s12920-023-01535-6
复制
发表时间：
2023-06-05
影响因子：
2.7
通讯作者：
中科院分区：
文献类型：
--
作者：
一些膀胱相关疾病，如膀胱尿路感染（UTI）和膀胱癌（BCa），在发病率和预后方面存在明显的六项差异。然而，这些性别差异背后的分子机制仍然没有完全理解。了解正常膀胱细胞中基因表达的性别差异有助于解决这些问题。我们首先收集了已发表的女性和男性正常人膀胱的单细胞RNA测序（scRNA-seq）数据，以绘制膀胱转录组景观。然后，基因本体论（GO）分析和基因集富集分析（GSEA），以确定在特定的细胞群体中发生变化的重要途径。使用Monocle 2软件包重建成纤维细胞的分化轨迹。此外，scMetabolism软件包用于分析单细胞水平的代谢活性，SCENIC软件包用于分析调控网络。总共有27，437个细胞通过了严格的质量控制，并根据经典标记物鉴定了人类膀胱中的八种主要细胞类型。基于性别的差异基因表达谱主要在人膀胱尿路上皮细胞、成纤维细胞、B细胞和T细胞中观察到。我们发现，男性的尿路上皮细胞表现出更高的生长速度。此外，女性成纤维细胞产生更多的细胞外基质，包括7个胶原基因，可能介导BCa进展。此外，结果显示，女性膀胱中的B细胞具有更多的B细胞激活信号和更高的免疫球蛋白基因表达。我们还发现，女性膀胱中的T细胞表现出更多的T细胞激活信号。这些细胞群的这些不同的生物学功能和特性可能与UTI和BCa的性别差异相关，并导致不同的疾病过程和结果。我们的研究为进一步研究人类膀胱中基于性别的生理和病理差异提供了合理的见解，这将有助于了解UTI和BCa的流行病学差异。在线版本包含补充材料，可通过10.1186/s12920-023-01535-6获得。
Some bladder-related diseases, such as bladder urinary tract infection (UTI) and bladder cancer (BCa), have significant six differences in incidence and prognosis. However, the molecular mechanisms underlying these sex differences are still not fully understood. Understanding the sex-biased differences in gene expression in normal bladder cells can help resolve these problems. We first collected published single-cell RNA sequencing (scRNA-seq) data of normal human bladders from females and males to map the bladder transcriptomic landscape. Then, Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) were used to determine the significant pathways that changed in the specific cell populations. The Monocle2 package was performed to reconstruct the differentiation trajectories of fibroblasts. In addition, the scMetabolism package was used to analyze the metabolic activity at the single-cell level, and the SCENIC package was used to analyze the regulatory network. In total, 27,437 cells passed stringent quality control, and eight main cell types in human bladder were identified according to classical markers. Sex-based differential gene expression profiles were mainly observed in human bladder urothelial cells, fibroblasts, B cells, and T cells. We found that urothelial cells in males demonstrated a higher growth rate. Moreover, female fibroblasts produced more extracellular matrix, including seven collagen genes that may mediate BCa progression. Furthermore, the results showed that B cells in female bladders exhibited more B-cell activated signals and a higher expression of immunoglobulin genes. We also found that T cells in female bladders exhibited more T-cell activated signals. These different biological functions and properties of these cell populations may correlate with sex differences in UTI and BCa, and result in different disease processes and outcomes. Our study provides reasonable insights for further studies of sex-based physiological and pathological disparities in the human bladder, which will contribute to the understanding of epidemiological differences in UTI and BCa. The online version contains supplementary material available at 10.1186/s12920-023-01535-6.
登录
查看更多内容
癌症相关成纤维细胞中 microRNA-149 的表观遗传沉默介导肿瘤微环境中前列腺素 E2/白细胞介素 6 信号传导
影响因子：
44.1
作者：
通讯作者：
--
影响因子：
16.6
作者：
Ou Q;Fang JQ;Zhang ZS;Chi Z;Fang J;Xu DY;Lu KZ;Qian MQ;Zhang DY;Guo JP;Gao W;Zhang NR;Pan JP
通讯作者：
Pan JP
影响因子：
50.3
作者：
Ma, Zikun;Li, Xiangdong;Liu, Zhuowei
通讯作者：
Liu, Zhuowei
DOI：
10.1073/pnas.2023216118
发表时间：
2021-08-17
影响因子：
11.1
作者：
Huang Z;Chen B;Liu X;Li H;Xie L;Gao Y;Duan R;Li Z;Zhang J;Zheng Y;Su W
通讯作者：
Su W
影响因子：
23.4
作者：
Choi W;Ochoa A;McConkey DJ;Aine M;Höglund M;Kim WY;Real FX;Kiltie AE;Milsom I;Dyrskjøt L;Lerner SP
通讯作者：
Lerner SP