Open AccessThe Interaction of the Wnt and Notch Pathways Modulates Natural Killer Versus T Cell Differentiation
Author(s) -
Aoyama Keisuke,
Delaney Colleen,
VarnumFinney Barbara,
Kohn Aimee D.,
Moon Randall T.,
Bernstein Irwin D.
Publication year - 2007
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0102
Subject(s) - wnt signaling pathway , notch signaling pathway , biology , cd38 , microbiology and biotechnology , wnt3a , haematopoiesis , signal transduction , cellular differentiation , stem cell , t cell , notch proteins , cd34 , immunology , immune system , gene , genetics
The Wnt and Notch signaling pathways have been independently shown to play a critical role in regulating hematopoietic cell fate decisions. We previously reported that induction of Notch signaling in human CD34 + CD38 − cord blood cells by culture with the Notch ligand Delta1 resulted in more cells with T or natural killer (NK) lymphoid precursor phenotype. Here, we show that addition of Wnt3a to Delta1 further increased the percentage of CD34 − CD7 + and CD34 − CD7 + cyCD3 + cells with increased expression of CD3 ε and preT α. In contrast, culture with Wnt3a alone did not increase generation of CD34 − CD7 + precursors or expression of CD3 ε or preT α gene. Furthermore, Wnt3a increased the amount of activated Notch1, suggesting that Wnt modulates Notch signaling by affecting Notch protein levels. In contrast, addition of a Wnt signaling inhibitor to Delta1 increased the percentage of CD56 + NK cells. Overall, these results demonstrate that regulation of Notch signaling by the Wnt pathway plays a critical role in differentiation of precursors along the early T or NK differentiation pathways. Disclosure of potential conflicts of interest is found at the end of this article.