An essential developmental checkpoint for production of the T cell lineage.
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.
Ikawa
Tomokatsu
T
Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.
Hirose
Satoshi
S
Masuda
Kyoko
K
Kakugawa
Kiyokazu
K
Satoh
Rumi
R
Shibano-Satoh
Asako
A
Kominami
Ryo
R
Katsura
Yoshimoto
Y
Kawamoto
Hiroshi
H
D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D018920:Coculture Techniques; D018507:Gene Expression Regulation, Developmental; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D015851:Interleukin-7 / Q000378:metabolism; D008099:Liver / Q000196:embryology; D038041:Lymphopoiesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
C511143:Bcl11b protein, mouse; D015851:Interleukin-7; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins