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Stage‐dependent molecular changes in Notch signaling are critical for normal human T cell development
Author(s) -
Taghon Tom,
Van de Walle Inge,
De Smet Greet,
De Smedt Magda,
Plum Jean
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.844.3
Subject(s) - notch signaling pathway , microbiology and biotechnology , cell fate determination , biology , cell growth , cell , t cell , signal transduction , immunology , genetics , transcription factor , immune system , gene
Notch signaling is one of the major drivers of T cell development. While the requirements for this pathway have been well established during mouse T cell development, its role in this developmental process in human is less clear. Here, using the OP9‐DL1 coculture system, we demonstrate that different levels of Notch activation, through different downstream molecular events, are required at the major developmental checkpoints of human T cell development. We show that these Notch driven events in human induce different developmental cell fate decisions compared to during mouse T cell development. Furthermore, through characterization of the β‐selection checkpoint in human T cell development, we demonstrate that Notch signaling is mainly required for proliferation of human thymocytes, but much less important for differentiation, in contrast to during similar stages of mouse T cell development. Thus, our results reveal stage‐dependent molecular changes in Notch signaling that are critical for normal human T cell development and fundamentally different compared to the mouse. This work was supported by the Belgian Science Policy, Research Foundation Flanders (FWO), Institute for Innovation of Science and Technology (IWT) and Concerted Research Activities (GOA).