Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

A cell atlas of human thymic development defines T cell repertoire formation

View ORCID ProfileJong-Eun Park, Rachel A. Botting, View ORCID ProfileCecilia Domínguez Conde, Dorin-Mirel Popescu, Marieke Lavaert, Daniel J. Kunz, Emily Stephenson, Roberta Ragazzini, Elizabeth Tuck, Anna Wilbrey-Clark, View ORCID ProfileJohn R. Ferdinand, Simone Webb, Daniel Maunder, Niels Vandamme, Krishnaa Mahbubani, Krzysztof Polanski, Lira Mamanova, Andrew Fuller, Andrew Filby, Gary Reynolds, David Dixon, Kourosh Saeb-Parsy, Steven Lisgo, Deborah Henderson, Roser Vento-Tormo, View ORCID ProfileKerstin B. Meyer, Yvan Saeys, Paola Bonfanti, Sam Behjati, Menna R. Clatworthy, Tom Taghon, Muzlifah Haniffa, View ORCID ProfileSarah A. Teichmann
doi: https://doi.org/10.1101/2020.01.28.911115
Jong-Eun Park
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jong-Eun Park
Rachel A. Botting
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cecilia Domínguez Conde
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Cecilia Domínguez Conde
Dorin-Mirel Popescu
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marieke Lavaert
Faculty of Medicine and Health Sciences, Department of Diagnostic Sciences, Ghent University, C. Heymanslaan 10, MRB2, Entrance 38, 9000 Ghent, BelgiumCancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel J. Kunz
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UKTheory of Condensed Matter Group, Cavendish Laboratory/Department of Physics, University of Cambridge, Cambridge CB3 0HE, UKThe Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emily Stephenson
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roberta Ragazzini
The Francis Crick Institute, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth Tuck
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna Wilbrey-Clark
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John R. Ferdinand
Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, United Kingdom, CB2 0QQ
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for John R. Ferdinand
Simone Webb
Faculty of Medicine and Health Sciences, Department of Diagnostic Sciences, Ghent University, C. Heymanslaan 10, MRB2, Entrance 38, 9000 Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel Maunder
Faculty of Medicine and Health Sciences, Department of Diagnostic Sciences, Ghent University, C. Heymanslaan 10, MRB2, Entrance 38, 9000 Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Niels Vandamme
Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, BelgiumDepartment of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Krishnaa Mahbubani
Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, United Kingdom, CB2 0QQ
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Krzysztof Polanski
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lira Mamanova
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew Fuller
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew Filby
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gary Reynolds
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Dixon
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kourosh Saeb-Parsy
Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, United Kingdom, CB2 0QQ
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven Lisgo
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Deborah Henderson
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roser Vento-Tormo
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kerstin B. Meyer
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kerstin B. Meyer
Yvan Saeys
Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, BelgiumDepartment of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paola Bonfanti
The Francis Crick Institute, London, UKGreat Ormond Street Institute of Child Health, University College London, London, UKInstitute of Immunity and Transplantation, University College London, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sam Behjati
Department of Haematology and Wellcome and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 2XY, UKDepartment of Paediatrics, University of Cambridge, Cambridge CB2 0SP, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Menna R. Clatworthy
Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, United Kingdom, CB2 0QQCambridge University Hospitals NHS Foundation Trust, United Kingdom, CB2 0QQ
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tom Taghon
Faculty of Medicine and Health Sciences, Department of Diagnostic Sciences, Ghent University, C. Heymanslaan 10, MRB2, Entrance 38, 9000 Ghent, BelgiumCancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: st9@sanger.ac.uk
Muzlifah Haniffa
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UKInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UKDepartment of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: st9@sanger.ac.uk
Sarah A. Teichmann
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UKTheory of Condensed Matter Group, Cavendish Laboratory/Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sarah A. Teichmann
  • For correspondence: st9@sanger.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We utilised single-cell RNA-sequencing (scRNA-seq) to create a cell census of the human thymus and to reconstruct T-cell differentiation trajectories and T-cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ novel CD8αα+ T-cell populations, thymic fibroblast subtypes and activated dendritic cell (aDC) states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and suggests later commitment of the CD8+ T-cell lineage. Taken together, our data provide a comprehensive atlas of the human thymus across the lifespan with new insights into human T-cell development.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted January 28, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
A cell atlas of human thymic development defines T cell repertoire formation
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
A cell atlas of human thymic development defines T cell repertoire formation
Jong-Eun Park, Rachel A. Botting, Cecilia Domínguez Conde, Dorin-Mirel Popescu, Marieke Lavaert, Daniel J. Kunz, Emily Stephenson, Roberta Ragazzini, Elizabeth Tuck, Anna Wilbrey-Clark, John R. Ferdinand, Simone Webb, Daniel Maunder, Niels Vandamme, Krishnaa Mahbubani, Krzysztof Polanski, Lira Mamanova, Andrew Fuller, Andrew Filby, Gary Reynolds, David Dixon, Kourosh Saeb-Parsy, Steven Lisgo, Deborah Henderson, Roser Vento-Tormo, Kerstin B. Meyer, Yvan Saeys, Paola Bonfanti, Sam Behjati, Menna R. Clatworthy, Tom Taghon, Muzlifah Haniffa, Sarah A. Teichmann
bioRxiv 2020.01.28.911115; doi: https://doi.org/10.1101/2020.01.28.911115
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
A cell atlas of human thymic development defines T cell repertoire formation
Jong-Eun Park, Rachel A. Botting, Cecilia Domínguez Conde, Dorin-Mirel Popescu, Marieke Lavaert, Daniel J. Kunz, Emily Stephenson, Roberta Ragazzini, Elizabeth Tuck, Anna Wilbrey-Clark, John R. Ferdinand, Simone Webb, Daniel Maunder, Niels Vandamme, Krishnaa Mahbubani, Krzysztof Polanski, Lira Mamanova, Andrew Fuller, Andrew Filby, Gary Reynolds, David Dixon, Kourosh Saeb-Parsy, Steven Lisgo, Deborah Henderson, Roser Vento-Tormo, Kerstin B. Meyer, Yvan Saeys, Paola Bonfanti, Sam Behjati, Menna R. Clatworthy, Tom Taghon, Muzlifah Haniffa, Sarah A. Teichmann
bioRxiv 2020.01.28.911115; doi: https://doi.org/10.1101/2020.01.28.911115

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (1647)
  • Biochemistry (2739)
  • Bioengineering (1907)
  • Bioinformatics (10243)
  • Biophysics (4183)
  • Cancer Biology (3218)
  • Cell Biology (4538)
  • Clinical Trials (135)
  • Developmental Biology (2840)
  • Ecology (4460)
  • Epidemiology (2041)
  • Evolutionary Biology (7231)
  • Genetics (5476)
  • Genomics (6813)
  • Immunology (2388)
  • Microbiology (7483)
  • Molecular Biology (2992)
  • Neuroscience (18584)
  • Paleontology (136)
  • Pathology (472)
  • Pharmacology and Toxicology (780)
  • Physiology (1149)
  • Plant Biology (2706)
  • Scientific Communication and Education (680)
  • Synthetic Biology (888)
  • Systems Biology (2846)
  • Zoology (468)