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Cited by 152T-cell and B-cell ImmunologyHematopoietic Stem Cell TransplantationDevelopmental Biology and Gene Regulation

The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential

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Luc, Sidinh, Luis, Tiago C, Boukarabila, Hanane, Macaulay, Iain C, Buza-Vidas, Natalija, Bouriez-Jones, Tiphaine, Lutteropp, Michael, Woll, Petter S +22 more·2012·Nature Immunology
DOI 10.1038/ni.2255PMC PMC3378629
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Abstract

The stepwise commitment from hematopoietic stem cells in the bone marrow to T lymphocyte-restricted progenitors in the thymus represents a paradigm for understanding the requirement for distinct extrinsic cues during different stages of lineage restriction from multipotent to lineage-restricted progenitors. However, the commitment stage at which progenitors migrate from the bone marrow to the thymus remains unclear. Here we provide functional and molecular evidence at the single-cell level that the earliest progenitors in the neonatal thymus had combined granulocyte-monocyte, T lymphocyte and B lymphocyte lineage potential but not megakaryocyte-erythroid lineage potential. These potentials were identical to those of candidate thymus-seeding progenitors in the bone marrow, which were closely related at the molecular level. Our findings establish the distinct lineage-restriction stage at which the T cell lineage-commitment process transits from the bone marrow to the remote thymus.

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  • ETP and DN2 cells can generate myeloid cells if removed from the thymus, whereas pro-T cells past PU.1 expression (DN3 or later) do not make myeloid cells under these conditions.

    “Whereas ETP and DN2 cells can generate myeloid cells if removed from the thymus, pro-T cells that have differentiated past the stage of PU.1 expression in the thymus (i.e., from the DN2 stage to the DN3 stage or later) do not make myeloid cells under these conditions”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [56]

    The Results section on ETPs and bone-marrow progenitors reports that DN2 cells retain T-cell and granulocyte–monocyte potential, while DN3 cells are the first T-cell-restricted progenitors (page unavailable). The Results on neonatal ETPs demonstrate myeloid potential in cultures outside the thymus. Our copy does not establish that the DN2-to-DN3 change coincides with the end of PU.1 expression or directly test DN2 and DN3 cells under the same removal conditions. (LLM, conf=0.87)

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Authors
Luc, S., Luis, T. C., Boukarabila, H., Macaulay, I. C., Buza-Vidas, N., Bouriez-Jones, T., Lutteropp, M., Woll, P. S., Loughran, S. J., Mead, A. J., Hultquist, A., Brown, J., Mizukami, T., Matsuoka, S., Ferry, H., Anderson, K., Duarte, S., Atkinson, D., Soneji, S., Domanski, A., Farley, A., Sanjuan-Pla, A., Carella, C., Patient, R., de Bruijn, M., Enver, T., Nerlov, C., Blackburn, C., Godin, I., & Jacobsen, S. E. W.
Affiliations
  • John Radcliffe Hospital (GB)
  • Lund University (SE)
  • University of Oxford (GB)
  • MRC Centre for Regenerative Medicine (GB)
  • European Molecular Biology Laboratory (IT)
  • Université Paris-Sud (FR)
Corresponding author
Jacobsen, Sten Eirik W
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2012-02-19
Volume
13
Issue
4
Pages
412-419
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/ni.2255
PMC
PMC3378629
OpenAlex
W2060690570
Cited by
152
References
4
Citations by year
2026: 2 · 2025: 8 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 9 · 2020: 5 · 2019: 9 · 2018: 14 · 2017: 14 · 2016: 11 · 2015: 14 · 2014: 13 · 2013: 21 · 2012: 8
FWCI
7.83
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Swedish Cancer Foundation
  • Leukaemia and Lymphoma Research
  • University of Oxford
  • Medical Research Council
  • Japan Society for the Promotion of Science (23791093)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
lineage restriction, neonatal thymus, hematopoietic stem cells, bone marrow, single-cell analysis, lineage commitment
MeSH terms
Animals, B-Lymphocytes, Cell Separation, Flow Cytometry, Hematopoietic Stem Cells, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, Thymus Gland, Cell Lineage, Oligonucleotide Array Sequence Analysis, Myeloid Cells, Mice, Precursor Cells, B-Lymphoid, Lymphoid Progenitor Cells, Real-Time Polymerase Chain Reaction

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