Requirement for Notch1 signals at sequential early stages of intrathymic T cell development.
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.
Tan
Joanne B
JB
Program in Developmental Biology, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 1X8, Canada.
Visan
Ioana
I
Yuan
Julie S
JS
Guidos
Cynthia J
CJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D016695:Glycosyltransferases / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000276:immunology*; D018183:Transplantation Chimera
D051792:Basic Helix-Loop-Helix Proteins; D016695:Glycosyltransferases; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C489734:Hes1 protein, mouse; C497762:Notch1 protein, mouse; C498392:Lfng protein, mouse