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Nat Immunol. 2005 Jul;6(7):671-9. Epub 2005 Jun 12.

Requirement for Notch1 signals at sequential early stages of intrathymic T cell development.

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Program in Developmental Biology, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 1X8, Canada.

Erratum in

  • Nat Immunol. 2005 Sep;6(9):954.


Signaling through the transmembrane Notch1 receptor directs thymus-seeding progenitors (TSPs) to suppress their B cell potential and 'choose' the T cell fate. Present paradigms suggest that TSPs are contained in the multipotent early T lineage precursor (ETP) subset of thymocytes. However, we show here that the B cell potential of ETPs was not augmented in microenvironments that limited Notch1 activation. Furthermore, low-threshold Notch1 signals suppressed B cell production by TSPs before they reached the ETP stage. Notch1 signals of a higher threshold were needed to drive proliferation of ETPs and development into CD4(+)CD8(+) double-positive thymocytes. Thus, TSPs can be differentiated from all previously identified early T cell progenitors by their robust B cell potential and exquisite sensitivity to Notch1 signals.

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