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2009-04-13

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/177169

CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha}gene expression in early human thymopoiesis and leukemia

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https://doi.org/10.1084/jem.20081922

Resum

Notch1 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.

Matèries

Expressió gènica, Leucèmia, Immunologia, Timus (Glàndula)

Matèries (anglès)

Gene expression, Leukemia, Immunology, Thymus

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Articles publicats en revistes (Ciències Fisiològiques)

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GONZÁLEZ-GARCÍA, Sara, GARCÍA-PEYDRÓ, Marina, MARTÍN-GAYO, Enrique, BALLESTAR TARÍN, Esteban, ESTELLER, Manel, BORNSTEIN, Rafael, POMPA, José luis de la, FERRANDO, Adolfo a., TORIBIO, María l.. CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha}gene expression in early human thymopoiesis and leukemia. _Journal of Experimental Medicine_. 2009. Vol. 206, núm. 4, pàgs. 779-791. [consulta: 24 de gener de 2026]. ISSN: 0022-1007. [Disponible a: https://hdl.handle.net/2445/177169]

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