The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Adult T-cell progenitors retain myeloid potential
Abstract
During haematopoiesis, pluripotent haematopoietic stem cells are sequentially restricted to give rise to a variety of lineage-committed progenitors. The classical model of haematopoiesis postulates that, in the first step of differentiation, the stem cell generates common myelo-erythroid progenitors and common lymphoid progenitors (CLPs). However, our previous studies in fetal mice showed that myeloid potential persists even as the lineage branches segregate towards T and B cells. We therefore proposed the 'myeloid-based' model of haematopoiesis, in which the stem cell initially generates common myelo-erythroid progenitors and common myelo-lymphoid progenitors. T-cell and B-cell progenitors subsequently arise from common myelo-lymphoid progenitors through myeloid-T and myeloid-B stages, respectively. However, it has been unclear whether this myeloid-based model is also valid for adult haematopoiesis. Here we provide clonal evidence that the early cell populations in the adult thymus contain progenitors that have lost the potential to generate B cells but retain substantial macrophage potential as well as T-cell, natural killer (NK)-cell and dendritic-cell potential. We also show that such T-cell progenitors can give rise to macrophages in the thymic environment in vivo. Our findings argue against the classical dichotomy model in which T cells are derived from CLPs; instead, they support the validity of the myeloid-based model for both adult and fetal haematopoiesis.
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“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 [41]
In the citing paper
“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 [41]
Citations
Cites
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T-cell apoptosis detected in situ during positive and negative selection in the thymus
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The earliest thymic progenitors for T cells possess myeloid lineage potential
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DETERMINANTS OF LYMPHOID-MYELOID LINEAGE DIVERSIFICATION
Laiosa, C. V., Stadtfeld, M., & Graf, T. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090742 · Cited by 265
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Redefinition of lymphoid progenitors
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Cited by
Sorted by citations
The genetic basis of early T-cell precursor acute lymphoblastic leukaemia
Zhang, J., Ding, L., Holmfeldt, L., Wu, G., Heatley, S. L., Payne-Turner, D., Easton, J., Chen, X., Wang, J., Rusch, M., et al. (2012) · Nature · doi:10.1038/nature10725 · Cited by 1,596
“The normal ETP, or double negative 1 (DN1) thymocyte retains the ability to differentiate into cells of both the T-cell and myeloid, but not B-cell, lineage”
BackgroundEarly T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia
Coustan‐Smith, E., Mullighan, C. G., Onciu, M. M., Behm, F. G., Raimondi, S. C., Pei, D., Cheng, C., Su, X., Rubnitz, J. E., Basso, G., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70314-0 · Cited by 1,012
Origin and evolution of the adaptive immune system: genetic events and selective pressures
Flajnik, M. F., & Kasahara, M. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2703 · Cited by 972
Hematopoiesis: a human perspective
Doulatov, S., Notta, F., Laurenti, E., & Dick, J. E. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.01.006 · Cited by 895
Comprehensive methylome map of lineage commitment from haematopoietic progenitors
Ji, H., Ehrlich, L. I. R., Seita, J., Murakami, P. N., Doi, A., Lindau, P., Lee, H.-J., Aryee, M. J., Irizarry, R. A., Kim, K., et al. (2010) · Nature · doi:10.1038/nature09367 · Cited by 636
Metadata
- Authors
- Wada, H., Masuda, K., Satoh, R., Kakugawa, K., Ikawa, T., Katsura, Y., & Kawamoto, H.
- Affiliations
- RIKEN (JP)
- Nihon University (JP)
- Corresponding author
- Kawamoto, Hiroshi
- Venue
- Nature
- Published
- 2008-04
- Volume
- 452
- Issue
- 7188
- Pages
- 768-772
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2047137615
- Cited by
- 368
- References
- 28
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 13 · 2023: 13 · 2022: 12 · 2021: 11 · 2020: 10 · 2019: 12 · 2018: 10 · 2017: 14 · 2016: 19 · 2015: 17 · 2014: 21 · 2013: 33 · 2012: 32
- FWCI
- 30.18
- 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 progenitors, common lymphoid progenitors, thymus, macrophage differentiation, natural killer cells, dendritic cells, lineage restriction, clonal analysis, hematopoietic stem cells
- MeSH terms
- Aging, Animals, B-Lymphocytes, Cells, Cultured, Dendritic Cells, Fetus, Hematopoiesis, Hematopoietic Stem Cells, Killer Cells, Natural, Macrophages, Models, Biological, T-Lymphocytes, Thymus Gland, Stromal Cells, Coculture Techniques, Cell Lineage, Myeloid Cells, Mice
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