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Science 329 (5987): 93-96

Copyright © 2010 by the American Association for the Advancement of Science

An Essential Developmental Checkpoint for Production of the T Cell Lineage

Tomokatsu Ikawa,1 Satoshi Hirose,2 Kyoko Masuda,1 Kiyokazu Kakugawa,1 Rumi Satoh,1 Asako Shibano-Satoh,1 Ryo Kominami,2 Yoshimoto Katsura,1,3 Hiroshi Kawamoto1,*

Abstract: In early T cell development, progenitors retaining the potential to generate myeloid and natural killer lineages are eventually determined to a specific T cell lineage. The molecular mechanisms that drive this determination step remain unclarified. We show that, when murine hematopoietic progenitors were cultured on immobilized Notch ligand DLL4 protein in the presence of a cocktail of cytokines including interleukin-7, progenitors developing toward T cells were arrested and the arrested cells entered a self-renewal cycle, maintaining non-T lineage potentials. Reduced concentrations of interleukin-7 promoted T cell lineage determination. A similar arrest and self-renewal of progenitors were observed in thymocytes of mice deficient in the transcription factor Bcl11b. Our study thus identifies the earliest checkpoint during T cell development and shows that it is Bcl11b-dependent.

1 Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.
2 Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.
3 Division of Cell Regeneration and Transplantation, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo 173-8610, Japan.

* To whom correspondence should be addressed. E-mail: kawamoto{at}rcai.riken.jp

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