Single-cell immune profiling reveals thymus-seeding populations, T cell commitment, and multilineage development in the human thymus

Science Immunology, vol. 7, pp. eade0182

Abstract

T cell development in the mouse thymus has been studied extensively, but less is known regarding T cell development in the human thymus. We used a combination of single-cell techniques and functional assays to perform deep immune profiling of human T cell development, focusing on the initial stages of prelineage commitment. We identified three thymus-seeding progenitor populations that also have counterparts in the bone marrow. In addition, we found that the human thymus physiologically supports the development of monocytes, dendritic cells, and NK cells, as well as limited development of B cells. These results are an important step toward monitoring and guiding regenerative therapies in patients after hematopoietic stem cell transplantation.

Authors 12

1. Martijn Cordes corresponding Aachen Department of Immunology, Leiden University Medical Center Leiden Computational Biology Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, Leiden, Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, Leiden, Netherlands

2. Kirsten Canté-Barrett corresponding Aachen Department of Immunology, Leiden University Medical Center Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW)

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, Leiden, Netherlands

   Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Netherlands

3. Erik B. van den Akker Aachen Leiden Computational Biology Center Molecular Epidemiology

   Leiden University Medical Center · Delft University of Technology

   Affiliation as printed

   Delft Bioinformatics Lab, Delft University of Technology, Delft, Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, Leiden, Netherlands

   Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands

4. Federico A. Moretti Aachen Department of Immunology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, Leiden, Netherlands

5. Szymon M. Kiełbasa Aachen Department of Biomedical Data Sciences

   Leiden University Medical Center

   Affiliation as printed

   Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands

6. Sandra A. Vloemans Aachen Department of Immunology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, Leiden, Netherlands

7. Laura García-Pérez Aachen Department of Immunology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, Leiden, Netherlands

8. Cristina Teodósio Aachen Department of Immunology, Leiden University Medical Center

   Consejo Superior de Investigaciones Científicas · Universidad de Salamanca · Leiden University Medical Center · Centro de Investigación del Cáncer · Instituto de Biología Molecular y Celular del Cáncer de Salamanca

   Affiliation as printed

   Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC, USAL-CSIC-FICUS), Department of Medicine, University of Salamanca, Salamanca, Spain

   Department of Immunology, Leiden University Medical Center, Leiden, Netherlands

9. Jacques J. M. van Dongen Aachen Department of Immunology, Leiden University Medical Center

   Consejo Superior de Investigaciones Científicas · Universidad de Salamanca · Leiden University Medical Center · Centro de Investigación del Cáncer · Instituto de Biología Molecular y Celular del Cáncer de Salamanca

   Affiliation as printed

   Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC, USAL-CSIC-FICUS), Department of Medicine, University of Salamanca, Salamanca, Spain

   Department of Immunology, Leiden University Medical Center, Leiden, Netherlands

10. Karin Pike‐Overzet Aachen Department of Immunology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Immunology, Leiden University Medical Center, Leiden, Netherlands

11. Marcel J. T. Reinders Aachen Leiden Computational Biology Center

    Leiden University Medical Center · Delft University of Technology

    Affiliation as printed

    Delft Bioinformatics Lab, Delft University of Technology, Delft, Netherlands

    Leiden Computational Biology Center, Leiden University Medical Center, Leiden, Netherlands

12. Frank J. T. Staal corresponding Aachen Department of Immunology, Leiden University Medical Center Department of Pediatrics, Leiden University Medical Center Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW)

    Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

    Affiliation as printed

    Department of Immunology, Leiden University Medical Center, Leiden, Netherlands

    Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands

    Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Netherlands