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Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymus

INTRODUCTION: Intrathymic 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 be...

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Autores principales: He, Han, Yao, Yingpeng, Tang, Lindong, Li, Yuhui, Li, Zongcheng, Liu, Bing, Lan, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10565475/
https://www.ncbi.nlm.nih.gov/pubmed/37828991
http://dx.doi.org/10.3389/fimmu.2023.1240859
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author He, Han
Yao, Yingpeng
Tang, Lindong
Li, Yuhui
Li, Zongcheng
Liu, Bing
Lan, Yu
author_facet He, Han
Yao, Yingpeng
Tang, Lindong
Li, Yuhui
Li, Zongcheng
Liu, Bing
Lan, Yu
author_sort He, Han
collection PubMed
description INTRODUCTION: Intrathymic 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. METHOD: In this study, we performed integrative single-cell analyses of thymocytes at distinct developmental stages. RESULTS: The 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. DISCUSSION: In 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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spelling pubmed-105654752023-10-12 Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymus He, Han Yao, Yingpeng Tang, Lindong Li, Yuhui Li, Zongcheng Liu, Bing Lan, Yu Front Immunol Immunology INTRODUCTION: Intrathymic 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. METHOD: In this study, we performed integrative single-cell analyses of thymocytes at distinct developmental stages. RESULTS: The 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. DISCUSSION: In 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. Frontiers Media S.A. 2023-09-27 /pmc/articles/PMC10565475/ /pubmed/37828991 http://dx.doi.org/10.3389/fimmu.2023.1240859 Text en Copyright © 2023 He, Yao, Tang, Li, Li, Liu and Lan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
He, Han
Yao, Yingpeng
Tang, Lindong
Li, Yuhui
Li, Zongcheng
Liu, Bing
Lan, Yu
Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymus
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10565475/
https://www.ncbi.nlm.nih.gov/pubmed/37828991
http://dx.doi.org/10.3389/fimmu.2023.1240859
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