An essential developmental checkpoint for production of the T cell lineage

Tomokatsu Ikawa, Satoshi Hirose, Kyoko Masuda, Kiyokazu Kakugawa, Rumi Satoh, Asako Shibano-Satoh, Ryo Kominami, Yoshimoto Katsura, Hiroshi Kawamoto

Research output: Contribution to journalArticlepeer-review

212 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)93-96
Number of pages4
JournalScience
Volume329
Issue number5987
DOIs
Publication statusPublished - 02-07-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Fingerprint

Dive into the research topics of 'An essential developmental checkpoint for production of the T cell lineage'. Together they form a unique fingerprint.

Cite this