Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymus
IntroductionIntrathymic T-cell development is a coordinated process accompanied by dynamic changes in gene expression. Although the transcriptome characteristics of developing T cells in both human fetal and postnatal thymus at single-cell resolution have been revealed recently, the differences betw...
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| Format: | Article |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1240859/full |
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| author | Han He Yingpeng Yao Yingpeng Yao Lindong Tang Yuhui Li Zongcheng Li Bing Liu Bing Liu Yu Lan |
| author_facet | Han He Yingpeng Yao Yingpeng Yao Lindong Tang Yuhui Li Zongcheng Li Bing Liu Bing Liu Yu Lan |
| author_sort | Han He |
| collection | DOAJ |
| description | IntroductionIntrathymic T-cell development is a coordinated process accompanied by dynamic changes in gene expression. Although the transcriptome characteristics of developing T cells in both human fetal and postnatal thymus at single-cell resolution have been revealed recently, the differences between human prenatal and postnatal thymocytes regarding the ontogeny and early events of T-cell development still remain obscure. Moreover, the transcriptional heterogeneity and posttranscriptional gene expression regulation such as alternative polyadenylation at different stages are also unknown.MethodIn this study, we performed integrative single-cell analyses of thymocytes at distinct developmental stages.ResultsThe subsets of prenatal CD4–CD8– double-negative (DN) cells, the most immature thymocytes responsible for T-cell lineage commitment, were characterized. By comprehensively comparing prenatal and postnatal DN cells, we revealed significant differences in some key gene expressions. Specifically, prenatal DN subpopulations exhibited distinct biological processes and markedly activated several metabolic programs that may be coordinated to meet the required bioenergetic demands. Although showing similar gene expression patterns along the developmental path, prenatal and postnatal thymocytes were remarkably varied regarding the expression dynamics of some pivotal genes for cell cycle, metabolism, signaling pathway, thymus homing, and T-cell commitment. Finally, we quantified the transcriptome-wide changes in alternative polyadenylation across T-cell development and found diverse preferences of polyadenylation site usage in divergent populations along the T-cell commitment trajectory.DiscussionIn summary, our results revealed transcriptional heterogeneity and a dynamic landscape of alternative polyadenylation during T-cell development in both human prenatal and postnatal thymus, providing a comprehensive resource for understanding T lymphopoiesis in human thymus. |
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| language | English |
| last_indexed | 2024-03-11T21:20:15Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-c70aee0ce84d4978a485ac716ee1c5932023-09-28T09:31:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12408591240859Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymusHan He0Yingpeng Yao1Yingpeng Yao2Lindong Tang3Yuhui Li4Zongcheng Li5Bing Liu6Bing Liu7Yu Lan8Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaBasic Medicine Postdoctoral Research Station, Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology, Senior Department of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology, Senior Department of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, ChinaIntroductionIntrathymic T-cell development is a coordinated process accompanied by dynamic changes in gene expression. Although the transcriptome characteristics of developing T cells in both human fetal and postnatal thymus at single-cell resolution have been revealed recently, the differences between human prenatal and postnatal thymocytes regarding the ontogeny and early events of T-cell development still remain obscure. Moreover, the transcriptional heterogeneity and posttranscriptional gene expression regulation such as alternative polyadenylation at different stages are also unknown.MethodIn this study, we performed integrative single-cell analyses of thymocytes at distinct developmental stages.ResultsThe subsets of prenatal CD4–CD8– double-negative (DN) cells, the most immature thymocytes responsible for T-cell lineage commitment, were characterized. By comprehensively comparing prenatal and postnatal DN cells, we revealed significant differences in some key gene expressions. Specifically, prenatal DN subpopulations exhibited distinct biological processes and markedly activated several metabolic programs that may be coordinated to meet the required bioenergetic demands. Although showing similar gene expression patterns along the developmental path, prenatal and postnatal thymocytes were remarkably varied regarding the expression dynamics of some pivotal genes for cell cycle, metabolism, signaling pathway, thymus homing, and T-cell commitment. Finally, we quantified the transcriptome-wide changes in alternative polyadenylation across T-cell development and found diverse preferences of polyadenylation site usage in divergent populations along the T-cell commitment trajectory.DiscussionIn summary, our results revealed transcriptional heterogeneity and a dynamic landscape of alternative polyadenylation during T-cell development in both human prenatal and postnatal thymus, providing a comprehensive resource for understanding T lymphopoiesis in human thymus.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1240859/fullhuman thymusscRNA-seqT cell developmentdouble-negative thymocytesalternative polyadenylation |
| spellingShingle | Han He Yingpeng Yao Yingpeng Yao Lindong Tang Yuhui Li Zongcheng Li Bing Liu Bing Liu Yu Lan Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymus Frontiers in Immunology human thymus scRNA-seq T cell development double-negative thymocytes alternative polyadenylation |
| title | Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymus |
| title_full | Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymus |
| title_fullStr | Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymus |
| title_full_unstemmed | Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymus |
| title_short | Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymus |
| title_sort | divergent molecular events underlying initial t cell commitment in human prenatal and postnatal thymus |
| topic | human thymus scRNA-seq T cell development double-negative thymocytes alternative polyadenylation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1240859/full |
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