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This paper reports on early hematopoietic lineage populations in SDF1 and SDF1 receptor (CXCR4) deficient mice, suggesting that this interaction is more important than the IL-7-IL-7R interaction for early developing B lineage cells in fetal liver. The failure of these mice to delineate a B/T restricted precursor in fetal liver may be consistent with earlier reports of the close association of B and myeloid lineages in fetal liver precursors, suggesting a different lineage branching in fetal development, in comparison to that in the bone marrow of adult animals.
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The authors demonstrate the continuing requirement for Pax5 expression through the pro-B stage, not just at the initial commitment stage, as demonstrated by a regulated Pax5 deletion system.
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Mikkola I., Heavey B., Horcher M., Busslinger M. Reversion of B cell commitment upon loss of Pax5 expression. Science. 297:2002;110-113 The authors demonstrate the continuing requirement for Pax5 expression through the pro-B stage, not just at the initial commitment stage, as demonstrated by a regulated Pax5 deletion system.
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The authors define the molecular pathway for B cell precursor growth inhibition by TGF-β. The authors report that TGF-β growth inhibition is mediated by the upregulation of Id3, which in turn acts to inhibit the function of E proteins in promoting survival of early B-lineage cells, thereby establishing a new role for E proteins.
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The authors demonstrate the crucial function of Notch-1 in signaling the T-cell fate, by analyzing the development of Notch-1 deficient precursors in the thymus. Such cells rather than developing along the T lineage, instead generate B cells in the thymus.
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Wilson A., MacDonald H.R., Radtke F. Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus. J. Exp. Med. 194:2001;1003-1012 The authors demonstrate the crucial function of Notch-1 in signaling the T-cell fate, by analyzing the development of Notch-1 deficient precursors in the thymus. Such cells rather than developing along the T lineage, instead generate B cells in the thymus.
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This is a further indication of the critical role of Notch-1 signaling in T-cell development. Inhibition of Notch-1 signaling by ectopic expression of lunatic fringe results in the re-direction of T-cell development along the B lineage in thymus.
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Koch U., Lacombe T.A., Holland D., Bowman J.L., Cohen B.L., Egan S.E., Guidos C.J. Subversion of the T/B lineage decision in the thymus by lunatic fringe-mediated inhibition of Notch-1. Immunity. 15:2001;225-236 This is a further indication of the critical role of Notch-1 signaling in T-cell development. Inhibition of Notch-1 signaling by ectopic expression of lunatic fringe results in the re-direction of T-cell development along the B lineage in thymus.
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The authors relay the unexpected finding that Deltex1, thought to be a positive modulator of Notch-1 function, instead acts to re-direct T-cell development in thymus along the B lineage, both in vivo and in vitro. Their data suggest that a balance between inductive and inhibitory signals converging on the Notch pathway serves to regulate the T/B lineage choice.
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Izon D.J., Aster J.C., He Y., Weng A., Karnell F.G., Patriub V., Xu L., Bakkour S., Rodriguez C., Allman D.et al. Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1. Immunity. 16:2002;231-243 The authors relay the unexpected finding that Deltex1, thought to be a positive modulator of Notch-1 function, instead acts to re-direct T-cell development in thymus along the B lineage, both in vivo and in vitro. Their data suggest that a balance between inductive and inhibitory signals converging on the Notch pathway serves to regulate the T/B lineage choice.
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This paper shows that WNT signaling can affect hematopoiesis indirectly, by acting on stromal cells to inhibit B-cell development in vitro. In contrast, cultures of early B-lineage cells without stromal cells were unaffected by the addition of Wnt-3a conditioned medium.
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Yamane T., Kunisada T., Tsukamoto H., Yamazaki H., Niwa H., Takada S., Hayashi S.I. Wnt signaling regulates hemopoiesis through stromal cells. J. Immunol. 167:2001;765-772 This paper shows that WNT signaling can affect hematopoiesis indirectly, by acting on stromal cells to inhibit B-cell development in vitro. In contrast, cultures of early B-lineage cells without stromal cells were unaffected by the addition of Wnt-3a conditioned medium.
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