Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection
Abstract Background 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-023-01535-6 |
| _version_ | 1797806416091676672 |
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| author | Ribao Wu Xiahong Teng Qiong Song Shuai Chen Lihui Wang Jinling Liao Chunlin Zou |
| author_facet | Ribao Wu Xiahong Teng Qiong Song Shuai Chen Lihui Wang Jinling Liao Chunlin Zou |
| author_sort | Ribao Wu |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-03-13T06:06:59Z |
| format | Article |
| id | doaj.art-1694dc9aa49d4f0db04cae5149c570f0 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-03-13T06:06:59Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-1694dc9aa49d4f0db04cae5149c570f02023-06-11T11:27:57ZengBMCBMC Medical Genomics1755-87942023-06-0116111110.1186/s12920-023-01535-6Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infectionRibao Wu0Xiahong Teng1Qiong Song2Shuai Chen3Lihui Wang4Jinling Liao5Chunlin Zou6Center for Translational Medicine, Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, School of Basic Medical Sciences, Guangxi Medical UniversitySchool of International Education, Guangxi Medical UniversityCenter for Translational Medicine, Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, School of Basic Medical Sciences, Guangxi Medical UniversityCenter for Translational Medicine, Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, School of Basic Medical Sciences, Guangxi Medical UniversityCenter for Translational Medicine, Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, School of Basic Medical Sciences, Guangxi Medical UniversityCenter for Genomic and Personalized Medicine, Guangxi Medical UniversityCenter for Translational Medicine, Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, School of Basic Medical Sciences, Guangxi Medical UniversityAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12920-023-01535-6ScRNA-seqSex-based differential geneUrinary tract infectionBladder cancerExtracellular matrix |
| spellingShingle | Ribao Wu Xiahong Teng Qiong Song Shuai Chen Lihui Wang Jinling Liao Chunlin Zou Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection BMC Medical Genomics ScRNA-seq Sex-based differential gene Urinary tract infection Bladder cancer Extracellular matrix |
| title | Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection |
| title_full | Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection |
| title_fullStr | Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection |
| title_full_unstemmed | Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection |
| title_short | Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection |
| title_sort | single cell rna sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection |
| topic | ScRNA-seq Sex-based differential gene Urinary tract infection Bladder cancer Extracellular matrix |
| url | https://doi.org/10.1186/s12920-023-01535-6 |
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