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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1440-1447.
Prepublished online as a Blood First Edition Paper on October 14, 2004; DOI 10.1182/blood-2004-08-3257.
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HEMATOPOIESIS
Notch ligands Delta1 and Jagged1 transmit distinct signals to T-cell precursors
Sophie M. Lehar,
James Dooley,
Andrew G. Farr, and
Michael J. Bevan
From the Department of Immunology, University of Washington, Seattle; Howard Hughes Medical Institute, Seattle, WA; and the Department of Biological Structure, University of Washington, Seattle.
Signaling through the Notch pathway plays an essential role in inducing T-lineage commitment and promoting the maturation of immature thymocytes. Using an in vitro culture system, we show that 2 different classes of Notch ligands, Jagged1 or Delta1, transmit distinct signals to T-cell progenitors. OP9 stromal cells expressing either Jagged1 or Delta1 inhibit the differentiation of DN1 thymocytes into the B-cell lineage, but only the Delta1-expressing stromal cells promote the proliferation and maturation of T-cell progenitors through the early double-negative (DN) stages of thymocyte development. Whereas the majority of bone marrow–derived stem cells do not respond to Jagged1 signals, T-cell progenitors respond to Jagged1 signals during a brief window of their development between the DN1 and DN3 stages of thymic development. During these stages, Jagged1 signals can influence the differentiation of immature thymocytes along the natural killer (NK) and   T-cell lineages.
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