Single-cell RNA sequencing reveals cell landscape following antimony exposure during spermatogenesis in Drosophila testes
Abstract Antimony (Sb), is thought to induce testicular toxicity, although this remains controversial. This study investigated the effects of Sb exposure during spermatogenesis in the Drosophila testis and the underlying transcriptional regulatory mechanism at single-cell resolution. Firstly, we fou...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-03-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01391-4 |
| _version_ | 1797865536611155968 |
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| author | Jun Yu Yangbo Fu Zhiran Li Qiuru Huang Juan Tang Chi Sun Peiyao Zhou Lei He Feiteng Sun Xinmeng Cheng Li Ji Hao Yu Yi Shi Zhifeng Gu Fei Sun Xinyuan Zhao |
| author_facet | Jun Yu Yangbo Fu Zhiran Li Qiuru Huang Juan Tang Chi Sun Peiyao Zhou Lei He Feiteng Sun Xinmeng Cheng Li Ji Hao Yu Yi Shi Zhifeng Gu Fei Sun Xinyuan Zhao |
| author_sort | Jun Yu |
| collection | DOAJ |
| description | Abstract Antimony (Sb), is thought to induce testicular toxicity, although this remains controversial. This study investigated the effects of Sb exposure during spermatogenesis in the Drosophila testis and the underlying transcriptional regulatory mechanism at single-cell resolution. Firstly, we found that flies exposed to Sb for 10 days led to dose-dependent reproductive toxicity during spermatogenesis. Protein expression and RNA levels were measured by immunofluorescence and quantitative real-time PCR (qRT-PCR). Single-cell RNA sequencing (scRNA-seq) was performed to characterize testicular cell composition and identify the transcriptional regulatory network after Sb exposure in Drosophila testes. scRNA-seq analysis revealed that Sb exposure influenced various testicular cell populations, especially in GSCs_to_Early_Spermatogonia and Spermatids clusters. Importantly, carbon metabolism was involved in GSCs/early spermatogonia maintenance and positively related with SCP-Containing Proteins, S-LAPs, and Mst84D signatures. Moreover, Seminal Fluid Proteins, Mst57D, and Serpin signatures were highly positively correlated with spermatid maturation. Pseudotime trajectory analysis revealed three novel states for the complexity of germ cell differentiation, and many novel genes (e.g., Dup98B) were found to be expressed in state-biased manners during spermatogenesis. Collectively, this study indicates that Sb exposure negatively impacts GSC maintenance and spermatid elongation, damaging spermatogenesis homeostasis via multiple signatures in Drosophila testes and therefore supporting Sb-mediated testicular toxicity. |
| first_indexed | 2024-04-09T23:10:46Z |
| format | Article |
| id | doaj.art-6114ae707493495c9dfe1fa22804df80 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-09T23:10:46Z |
| publishDate | 2023-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-6114ae707493495c9dfe1fa22804df802023-03-22T10:25:29ZengNature Publishing GroupCell Death Discovery2058-77162023-03-019111410.1038/s41420-023-01391-4Single-cell RNA sequencing reveals cell landscape following antimony exposure during spermatogenesis in Drosophila testesJun Yu0Yangbo Fu1Zhiran Li2Qiuru Huang3Juan Tang4Chi Sun5Peiyao Zhou6Lei He7Feiteng Sun8Xinmeng Cheng9Li Ji10Hao Yu11Yi Shi12Zhifeng Gu13Fei Sun14Xinyuan Zhao15Institute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityDepartment of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong UniversityDepartment of Geriatrics, Affiliated Hospital of Nantong University, Nantong UniversityDepartment of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong UniversityInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityDepartment of Rheumatology, Affiliated Hospital of Nantong University, Nantong UniversityInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityDepartment of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong UniversityAbstract Antimony (Sb), is thought to induce testicular toxicity, although this remains controversial. This study investigated the effects of Sb exposure during spermatogenesis in the Drosophila testis and the underlying transcriptional regulatory mechanism at single-cell resolution. Firstly, we found that flies exposed to Sb for 10 days led to dose-dependent reproductive toxicity during spermatogenesis. Protein expression and RNA levels were measured by immunofluorescence and quantitative real-time PCR (qRT-PCR). Single-cell RNA sequencing (scRNA-seq) was performed to characterize testicular cell composition and identify the transcriptional regulatory network after Sb exposure in Drosophila testes. scRNA-seq analysis revealed that Sb exposure influenced various testicular cell populations, especially in GSCs_to_Early_Spermatogonia and Spermatids clusters. Importantly, carbon metabolism was involved in GSCs/early spermatogonia maintenance and positively related with SCP-Containing Proteins, S-LAPs, and Mst84D signatures. Moreover, Seminal Fluid Proteins, Mst57D, and Serpin signatures were highly positively correlated with spermatid maturation. Pseudotime trajectory analysis revealed three novel states for the complexity of germ cell differentiation, and many novel genes (e.g., Dup98B) were found to be expressed in state-biased manners during spermatogenesis. Collectively, this study indicates that Sb exposure negatively impacts GSC maintenance and spermatid elongation, damaging spermatogenesis homeostasis via multiple signatures in Drosophila testes and therefore supporting Sb-mediated testicular toxicity.https://doi.org/10.1038/s41420-023-01391-4 |
| spellingShingle | Jun Yu Yangbo Fu Zhiran Li Qiuru Huang Juan Tang Chi Sun Peiyao Zhou Lei He Feiteng Sun Xinmeng Cheng Li Ji Hao Yu Yi Shi Zhifeng Gu Fei Sun Xinyuan Zhao Single-cell RNA sequencing reveals cell landscape following antimony exposure during spermatogenesis in Drosophila testes Cell Death Discovery |
| title | Single-cell RNA sequencing reveals cell landscape following antimony exposure during spermatogenesis in Drosophila testes |
| title_full | Single-cell RNA sequencing reveals cell landscape following antimony exposure during spermatogenesis in Drosophila testes |
| title_fullStr | Single-cell RNA sequencing reveals cell landscape following antimony exposure during spermatogenesis in Drosophila testes |
| title_full_unstemmed | Single-cell RNA sequencing reveals cell landscape following antimony exposure during spermatogenesis in Drosophila testes |
| title_short | Single-cell RNA sequencing reveals cell landscape following antimony exposure during spermatogenesis in Drosophila testes |
| title_sort | single cell rna sequencing reveals cell landscape following antimony exposure during spermatogenesis in drosophila testes |
| url | https://doi.org/10.1038/s41420-023-01391-4 |
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