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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 potential1, 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-2. Our results indicate that alternative models for lineage commitment during haematopoiesis must be considered.

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Figure 1: ETPs have myeloid lineage potential.
Figure 2: Characterization of ETP-derived myeloid cells.
Figure 3: Thymic granulocytes possess antigen receptor gene rearrangements.

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Acknowledgements

We thank C. Bassing, M. Carroll, B. Schwarz and J. Thompson for advice. This work was supported by a grant from the NIH and a Scholar Award from the Leukemia and Lymphoma Society (A.B.) and an institutional training grant from NCI (J.J.B).

Author Contributions J.J.B. performed the majority of the experimental work. J.J.B. and A.B. together planned the project, analysed data and prepared the manuscript.

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Correspondence to Avinash Bhandoola.

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Bell, J., Bhandoola, A. The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature 452, 764–767 (2008). https://doi.org/10.1038/nature06840

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