Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development

Intrathymic differentiation of T lymphocytes begins as early as intrauterine stage, yet the T cell lineage decisions of human fetal thymocytes at different gestational ages are not currently understood. Here, we performed integrative single-cell analyses of thymocytes across gestational ages. We ide...

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Main Authors: Yuchen Li, Weihong Zeng, Tong Li, Yanyan Guo, Guangyong Zheng, Xiaoying He, Lilian Bai, Guolian Ding, Li Jin, Xinmei Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2021.679616/full
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author Yuchen Li
Yuchen Li
Yuchen Li
Weihong Zeng
Weihong Zeng
Weihong Zeng
Tong Li
Tong Li
Tong Li
Yanyan Guo
Yanyan Guo
Yanyan Guo
Guangyong Zheng
Xiaoying He
Xiaoying He
Lilian Bai
Lilian Bai
Lilian Bai
Guolian Ding
Guolian Ding
Guolian Ding
Li Jin
Li Jin
Xinmei Liu
Xinmei Liu
Xinmei Liu
author_facet Yuchen Li
Yuchen Li
Yuchen Li
Weihong Zeng
Weihong Zeng
Weihong Zeng
Tong Li
Tong Li
Tong Li
Yanyan Guo
Yanyan Guo
Yanyan Guo
Guangyong Zheng
Xiaoying He
Xiaoying He
Lilian Bai
Lilian Bai
Lilian Bai
Guolian Ding
Guolian Ding
Guolian Ding
Li Jin
Li Jin
Xinmei Liu
Xinmei Liu
Xinmei Liu
author_sort Yuchen Li
collection DOAJ
description Intrathymic differentiation of T lymphocytes begins as early as intrauterine stage, yet the T cell lineage decisions of human fetal thymocytes at different gestational ages are not currently understood. Here, we performed integrative single-cell analyses of thymocytes across gestational ages. We identified conserved candidates underlying the selection of T cell receptor (TCR) lineages in different human fetal stages. The trajectory of early thymocyte commitment during fetal growth was also characterized. Comparisons with mouse data revealed conserved and species-specific transcriptional dynamics of thymocyte proliferation, apoptosis and selection. Genome-wide association study (GWAS) data associated with multiple autoimmune disorders were analyzed to characterize susceptibility genes that are highly expressed at specific stages during fetal thymocyte development. In summary, our integrative map describes previously underappreciated aspects of human thymocyte development, and provides a comprehensive reference for understanding T cell lymphopoiesis in a self-tolerant and functional adaptive immune system.
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spelling doaj.art-606aae261f194f01a2442427e33713fc2022-12-21T18:23:37ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-07-011210.3389/fgene.2021.679616679616Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte DevelopmentYuchen Li0Yuchen Li1Yuchen Li2Weihong Zeng3Weihong Zeng4Weihong Zeng5Tong Li6Tong Li7Tong Li8Yanyan Guo9Yanyan Guo10Yanyan Guo11Guangyong Zheng12Xiaoying He13Xiaoying He14Lilian Bai15Lilian Bai16Lilian Bai17Guolian Ding18Guolian Ding19Guolian Ding20Li Jin21Li Jin22Xinmei Liu23Xinmei Liu24Xinmei Liu25International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Disease, Shanghai, ChinaResearch Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, ChinaInternational Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Disease, Shanghai, ChinaResearch Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, ChinaInternational Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Disease, Shanghai, ChinaResearch Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, ChinaInternational Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Disease, Shanghai, ChinaResearch Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, ChinaBio-Med Big Data Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, ChinaInternational Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Disease, Shanghai, ChinaInternational Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Disease, Shanghai, ChinaResearch Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Disease, Shanghai, ChinaResearch Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, ChinaObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Disease, Shanghai, ChinaObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Disease, Shanghai, ChinaResearch Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, ChinaObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, ChinaIntrathymic differentiation of T lymphocytes begins as early as intrauterine stage, yet the T cell lineage decisions of human fetal thymocytes at different gestational ages are not currently understood. Here, we performed integrative single-cell analyses of thymocytes across gestational ages. We identified conserved candidates underlying the selection of T cell receptor (TCR) lineages in different human fetal stages. The trajectory of early thymocyte commitment during fetal growth was also characterized. Comparisons with mouse data revealed conserved and species-specific transcriptional dynamics of thymocyte proliferation, apoptosis and selection. Genome-wide association study (GWAS) data associated with multiple autoimmune disorders were analyzed to characterize susceptibility genes that are highly expressed at specific stages during fetal thymocyte development. In summary, our integrative map describes previously underappreciated aspects of human thymocyte development, and provides a comprehensive reference for understanding T cell lymphopoiesis in a self-tolerant and functional adaptive immune system.https://www.frontiersin.org/articles/10.3389/fgene.2021.679616/fullfetal thymushuman and murinesingle-cell RNA-seqT lymphopoiesistranscriptional dynamics
spellingShingle Yuchen Li
Yuchen Li
Yuchen Li
Weihong Zeng
Weihong Zeng
Weihong Zeng
Tong Li
Tong Li
Tong Li
Yanyan Guo
Yanyan Guo
Yanyan Guo
Guangyong Zheng
Xiaoying He
Xiaoying He
Lilian Bai
Lilian Bai
Lilian Bai
Guolian Ding
Guolian Ding
Guolian Ding
Li Jin
Li Jin
Xinmei Liu
Xinmei Liu
Xinmei Liu
Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development
Frontiers in Genetics
fetal thymus
human and murine
single-cell RNA-seq
T lymphopoiesis
transcriptional dynamics
title Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development
title_full Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development
title_fullStr Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development
title_full_unstemmed Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development
title_short Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development
title_sort integrative single cell transcriptomic analysis of human fetal thymocyte development
topic fetal thymus
human and murine
single-cell RNA-seq
T lymphopoiesis
transcriptional dynamics
url https://www.frontiersin.org/articles/10.3389/fgene.2021.679616/full
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