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 cells1,2,3,4,5,6. We therefore proposed the ‘myeloid-based’ model of haematopoiesis7,8, 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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We thank P. Burrows, W. van Ewijk and W. T. V. Germeraad for critical reading of the manuscript, and O. Kawamoto for valuable advise.
Author Contributions H.W. performed most of experiments, with the assistance of R.S. and K.K. for immunohistochemical analysis and stromal cell co-cultures, respectively. Experiments shown in Fig. 1 and Supplementary Figs 2 and 3 were performed by K.M., and those in Supplementary Fig. 4d by T.I. Y.K. gave critical advice and comments in designing the experiments and writing the paper. H.K. designed the experiments and wrote the paper.
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Wada, H., Masuda, K., Satoh, R. et al. Adult T-cell progenitors retain myeloid potential. Nature 452, 768–772 (2008). https://doi.org/10.1038/nature06839
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