The earliest thymic progenitors for T cells possess myeloid lineage potential
Abstract
There exists controversy over the nature of haematopoietic progenitors of T cells. Most T cells develop in the thymus, but the lineage potential of thymus-colonizing progenitors is unknown. One approach to resolving this question is to determine the lineage potentials of the earliest thymic progenitors (ETPs). Previous work has shown that ETPs possess T and natural killer lymphoid potentials, and rare subsets of ETPs also possess B lymphoid potential, suggesting an origin from lymphoid-restricted progenitor cells. However, whether ETPs also possess myeloid potential is unknown. Here we show that nearly all ETPs in adult mice possess both T and myeloid potential in clonal assays. The existence of progenitors possessing T and myeloid potential within the thymus is incompatible with the current dominant model of haematopoiesis, in which T cells are proposed to arise from lymphoid-. Our results indicate that alternative models for lineage commitment during haematopoiesis must be considered.
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In mouse, natural loss of access to dendritic cell and granulocyte programs agrees with the timing of PU.1 downregulation.
“there is good agreement between the cells' natural loss of access to the dendritic cell and granulocyte programs, on the one hand, and the timing of PU.1 downregulation, on the other hand (33, 39–42).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [40]
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 [40]
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Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development
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- Authors
- Bell, J. J., & Bhandoola, A.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Bhandoola, Avinash
- ORCID
- Bhandoola, Avinash
- Venue
- Nature
- Published
- 2008-04
- Volume
- 452
- Issue
- 7188
- Pages
- 764-767
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2119709204
- Cited by
- 460
- References
- 5
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 19 · 2023: 11 · 2022: 15 · 2021: 13 · 2020: 12 · 2019: 24 · 2018: 22 · 2017: 20 · 2016: 26 · 2015: 16 · 2014: 28 · 2013: 38 · 2012: 39
- FWCI
- 34.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- T cell development, hematopoiesis, common lymphoid progenitors, natural killer cells, dendritic cells, lineage commitment, thymus, B-cell lineage
- MeSH terms
- Animals, Cells, Cultured, Dendritic Cells, Female, Granulocytes, Hematopoiesis, Hematopoietic Stem Cells, Macrophages, Models, Biological, T-Lymphocytes, Thymus Gland, Stromal Cells, Coculture Techniques, Cell Lineage, Myeloid Cells, Mice
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