Two waves of distinct hematopoietic progenitor cells colonize the fetal thymus
Abstract
The generation of T cells depends on the migration of hematopoietic progenitor cells to the thymus throughout life. The identity of the thymus-settling progenitor cells has been a matter of considerable debate. Here we found that thymopoiesis was initiated by a first wave of T cell lineage-restricted progenitor cells with limited capacity for population expansion but accelerated differentiation into mature T cells. They gave rise to αβ and γδ T cells that constituted Vγ3(+) dendritic epithelial T cells. Thymopoiesis was subsequently maintained by less-differentiated progenitor cells that retained the potential to develop into B cells and myeloid cells. In that second wave, which started before birth, progenitor cells had high proliferative capacity but delayed differentiation capacity and no longer gave rise to embryonic γδ T cells. Our work reconciles conflicting hypotheses on the nature of thymus-settling progenitor cells.
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The first wave of T cell development in the fetus is now thought to arise from these non-stem-cell precursors in the yolk sac.
“The first wave of T cell development in the fetus is now thought to arise from these non-stem-cell precursors in the yolk sac (132, 133).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [133]
The earliest fetal thymocytes are different from later waves of developing thymocytes in their abilities to generate particular classes of TCRγδ cells and in their extremely fast differentiation kinetics, both in vivo and in fetal thymic organ culture or stromal coculture systems.
“It has long been recognized that the earliest fetal thymocytes are different from later waves of developing thymocytes in terms of their abilities to generate particular classes of TCRγδ cells (134) and in terms of their extremely fast differentiation kinetics, both in vivo and in fetal thymic organ culture or stromal coculture systems (104, 133, 135).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [133]
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T/B lineage choice occurs prior to intrathymic Notch signaling
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Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development
Rothenberg, E. V., Hosokawa, H., & Ungerbäck, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00228 · Cited by 99 · see citing works
“It has long been recognized that the earliest fetal thymocytes are different from later waves of developing thymocytes in terms of their abilities to generate particular classes of TCRγδ cells (134) and in terms of their extremely fast differentiation kinetics, both in vivo and in fetal thymic organ culture or stromal…”
Background
- Authors
- Ramond, C., Berthault, C., Burlen-Defranoux, O., de Sousa, A. P., Guy-Grand, D., Vieira, P., Pereira, P., & Cumano, A.
- Affiliations
- Inserm (FR)
- Corresponding author
- Cumano, Ana
- Venue
- Nature Immunology
- Published
- 2013-12-08
- Volume
- 15
- Issue
- 1
- Pages
- 27-35
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W1996893147
- Cited by
- 110
- References
- 7
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 10 · 2023: 9 · 2022: 11 · 2021: 10 · 2020: 8 · 2019: 11 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 9 · 2014: 6
- FWCI
- 4.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- 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
- thymus colonization, hematopoietic progenitor cells, thymopoiesis, fetal thymus, T cell lineage, B-cell lineage, alpha beta T cells, γδ T cells, progenitor cell differentiation, progenitor cell proliferation, embryonic development
- MeSH terms
- Animals, Animals, Newborn, Cell Differentiation, Cell Line, Cells, Cultured, Flow Cytometry, Hematopoietic Stem Cells, Mice, Inbred C57BL, T-Lymphocytes, Thymus Gland, Time Factors, Receptors, Antigen, T-Cell, gamma-delta, Receptors, Antigen, T-Cell, alpha-beta, Mice, Knockout, Gene Expression Regulation, Developmental, Cell Lineage, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Mice, fms-Like Tyrosine Kinase 3, Interleukin-7 Receptor alpha Subunit, Transcriptome, Thymocytes
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