Comparative transcriptome analysis of T lymphocyte subpopulations and identification of critical regulators defining porcine thymocyte identity
IntroductionThe development and migration of T cells in the thymus and peripheral tissues are crucial for maintaining adaptive immunity in mammals. However, the regulatory mechanisms underlying T cell development and thymocyte identity formation in pigs remain largely underexplored. MethodHere, by i...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1339787/full |
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| author | Pingping Han Wei Zhang Daoyuan Wang Yalan Wu Xinyun Li Xinyun Li Shuhong Zhao Shuhong Zhao Mengjin Zhu Mengjin Zhu |
| author_facet | Pingping Han Wei Zhang Daoyuan Wang Yalan Wu Xinyun Li Xinyun Li Shuhong Zhao Shuhong Zhao Mengjin Zhu Mengjin Zhu |
| author_sort | Pingping Han |
| collection | DOAJ |
| description | IntroductionThe development and migration of T cells in the thymus and peripheral tissues are crucial for maintaining adaptive immunity in mammals. However, the regulatory mechanisms underlying T cell development and thymocyte identity formation in pigs remain largely underexplored. MethodHere, by integrating bulk and single-cell RNA-sequencing data, we investigated regulatory signatures of porcine thymus and lymph node T cells. ResultsThe comparison of T cell subpopulations derived from porcine thymus and lymph nodes revealed that their transcriptomic differences were influenced more by tissue origin than by T cell phenotypes, and that lymph node cells exhibited greater transcriptional diversity than thymocytes. Through weighted gene co-expression network analysis (WGCNA), we identified the key modules and candidate hub genes regulating the heterogeneity of T cell subpopulations. Further, we integrated the porcine thymocyte dataset with peripheral blood mononuclear cell (PBMC) dataset to systematically compare transcriptomic differences between T cell types from different tissues. Based on single-cell datasets, we further identified the key transcription factors (TFs) responsible for maintaining porcine thymocyte identity and unveiled that these TFs coordinately regulated the entire T cell development process. Finally, we performed GWAS of cell type-specific differentially expressed genes (DEGs) and 30 complex traits, and found that the DEGs in thymus-related and peripheral blood-related cell types, especially CD4_SP cluster and CD8-related cluster, were significantly associated with pig productive and reproductive traits. DiscussionOur findings provide an insight into T cell development and lay a foundation for further exploring the porcine immune system and genetic mechanisms underlying complex traits in pigs. |
| first_indexed | 2024-03-08T05:13:32Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T05:13:32Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-cb6d0e1b8bb34ee9ae1e2491fc45510d2024-02-07T04:56:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13397871339787Comparative transcriptome analysis of T lymphocyte subpopulations and identification of critical regulators defining porcine thymocyte identityPingping Han0Wei Zhang1Daoyuan Wang2Yalan Wu3Xinyun Li4Xinyun Li5Shuhong Zhao6Shuhong Zhao7Mengjin Zhu8Mengjin Zhu9Key Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, ChinaKey Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, ChinaKey Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, ChinaKey Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, ChinaKey Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, ChinaKey Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, ChinaKey Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, ChinaIntroductionThe development and migration of T cells in the thymus and peripheral tissues are crucial for maintaining adaptive immunity in mammals. However, the regulatory mechanisms underlying T cell development and thymocyte identity formation in pigs remain largely underexplored. MethodHere, by integrating bulk and single-cell RNA-sequencing data, we investigated regulatory signatures of porcine thymus and lymph node T cells. ResultsThe comparison of T cell subpopulations derived from porcine thymus and lymph nodes revealed that their transcriptomic differences were influenced more by tissue origin than by T cell phenotypes, and that lymph node cells exhibited greater transcriptional diversity than thymocytes. Through weighted gene co-expression network analysis (WGCNA), we identified the key modules and candidate hub genes regulating the heterogeneity of T cell subpopulations. Further, we integrated the porcine thymocyte dataset with peripheral blood mononuclear cell (PBMC) dataset to systematically compare transcriptomic differences between T cell types from different tissues. Based on single-cell datasets, we further identified the key transcription factors (TFs) responsible for maintaining porcine thymocyte identity and unveiled that these TFs coordinately regulated the entire T cell development process. Finally, we performed GWAS of cell type-specific differentially expressed genes (DEGs) and 30 complex traits, and found that the DEGs in thymus-related and peripheral blood-related cell types, especially CD4_SP cluster and CD8-related cluster, were significantly associated with pig productive and reproductive traits. DiscussionOur findings provide an insight into T cell development and lay a foundation for further exploring the porcine immune system and genetic mechanisms underlying complex traits in pigs.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1339787/fullcomparative transcriptomeT cell developmentco-expression analysisgene regulatory networktranscription factorGWAS |
| spellingShingle | Pingping Han Wei Zhang Daoyuan Wang Yalan Wu Xinyun Li Xinyun Li Shuhong Zhao Shuhong Zhao Mengjin Zhu Mengjin Zhu Comparative transcriptome analysis of T lymphocyte subpopulations and identification of critical regulators defining porcine thymocyte identity Frontiers in Immunology comparative transcriptome T cell development co-expression analysis gene regulatory network transcription factor GWAS |
| title | Comparative transcriptome analysis of T lymphocyte subpopulations and identification of critical regulators defining porcine thymocyte identity |
| title_full | Comparative transcriptome analysis of T lymphocyte subpopulations and identification of critical regulators defining porcine thymocyte identity |
| title_fullStr | Comparative transcriptome analysis of T lymphocyte subpopulations and identification of critical regulators defining porcine thymocyte identity |
| title_full_unstemmed | Comparative transcriptome analysis of T lymphocyte subpopulations and identification of critical regulators defining porcine thymocyte identity |
| title_short | Comparative transcriptome analysis of T lymphocyte subpopulations and identification of critical regulators defining porcine thymocyte identity |
| title_sort | comparative transcriptome analysis of t lymphocyte subpopulations and identification of critical regulators defining porcine thymocyte identity |
| topic | comparative transcriptome T cell development co-expression analysis gene regulatory network transcription factor GWAS |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1339787/full |
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