González-García, SaraGarcía-Peydró, MarinaMartín-Gayo, EnriqueBallestar Tarín, EstebanEsteller, Manel, 1968-Bornstein, RafaelPompa, José Luis de laFerrando, Adolfo A.Toribio, María L.2021-05-122021-05-122009-04-130022-1007https://hdl.handle.net/2445/177169Notch1 activation is essential for T-lineage specification of lymphomyeloid progenitors seeding the thymus. Progression along the T cell lineage further requires cooperative signaling provided by the interleukin 7 receptor (IL-7R), but the molecular mechanisms responsible for the dynamic and lineage-specific regulation of IL-7R during thymopoiesis are unknown. We show that active Notch1 binds to a conserved CSL-binding site in the human IL7R gene promoter and critically regulates IL7R transcription and IL-7R alpha chain (IL-7Ralpha) expression via the CSL-MAML complex. Defective Notch1 signaling selectively impaired IL-7Ralpha expression in T-lineage cells, but not B-lineage cells, and resulted in a compromised expansion of early human developing thymocytes, which was rescued upon ectopic IL-7Ralpha expression. The pathological implications of these findings are demonstrated by the regulation of IL-7Ralpha expression downstream of Notch1 in T cell leukemias. Thus, Notch1 controls early T cell development, in part by regulating the stage- and lineage-specific expression of IL-7Ralpha.13 p.application/pdfeng(c) Rockefeller University Press, 2009Expressió gènicaLeucèmiaImmunologiaTimus (Glàndula)Gene expressionLeukemiaImmunologyThymusinfo:eu-repo/semantics/article7002242021-05-12info:eu-repo/semantics/openAccess19349467