Nature 452, 768-772 (10 April 2008) | doi:10.1038/nature06839; Received 27 October 2007; Accepted 15 February 2008

Adult T-cell progenitors retain myeloid potential

Haruka Wada1,3, Kyoko Masuda1,3, Rumi Satoh1, Kiyokazu Kakugawa1, Tomokatsu Ikawa1, Yoshimoto Katsura1,2 & Hiroshi Kawamoto1

  1. Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan
  2. Division of Cell Regeneration and Transplantation, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo 173-8610, Japan
  3. Present addresses: Division of Bioregulation Research, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki 216-8512, Japan (H.W.); Institute of Molecular Medicine and Genetics, University of Georgia, GA 30602, USA (K.M.).

Correspondence to: Hiroshi Kawamoto1 Correspondence and requests for materials should be addressed to H.K. (Email: kawamoto@rcai.riken.jp).

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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