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+ (LSK) population that has lymphoid-myeloid but no MegE differentiation potential, called LMPPs. It challenges the classic lineage differentiation model and raises the possibility that GM cells can be generated by way of two separate routes: one through CMPs and another through LMPPs.
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+ early progenitors were found to retain MegE potential, suggesting that the restriction of MegE potential is not the first lineage differentiation step.
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Using CCR9-GFP mice, this study identified a multipotent precursor present in bone marrow, blood and thymus. Single cells of the precursor give rise to T, B and dendritic cells. This newly identified cell subset, termed thymic multipotent precursor (TMP), represents the earliest T-cell progenitor in the postnatal thymus.
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Benz C., and Bleul C.C. A multipotent precursor in the thymus maps to the branching point of the T versus B lineage decision. J Exp Med 202 (2005) 21-31. Using CCR9-GFP mice, this study identified a multipotent precursor present in bone marrow, blood and thymus. Single cells of the precursor give rise to T, B and dendritic cells. This newly identified cell subset, termed thymic multipotent precursor (TMP), represents the earliest T-cell progenitor in the postnatal thymus.
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The earliest thymic progenitors in adults are restricted to T, NK, and dendritic cell lineage and have a potential to form more diverse TCRβ chains than fetal progenitors
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PU.1 is not strictly required for B cell development and its absence induces a B-2 to B-1 cell switch
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-/- fetal liver cultures, showing that the gene is not strictly required for B-cell commitment. However, B-cell formation with the mutant cells occurs at low efficiencies and delayed kinetics compared with wild-type cells, indicating that PU.1 facilitates B-cell development.
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27
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33846593911
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A two-step, PU.1-dependent, mechanism for developmentally regulated chromatin remodelling and transcription of the c-fms gene
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Utilizing PU.1-deficient myeloid progenitors, this study suggests a two-step mechanism by PU.1 controls c-fms gene activation during development. The factor first binds to the c-fms promoter region to maintain its primed status in progenitor cells. It then binds to the enhancer region, together with other factors, to fully activate c-fms expression in differentiated myeloid cells.
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Krysinska H., Hoogenkamp M., Ingram R., Wilson N., Tagoh H., Laslo P., Singh H., and Bonifer C. A two-step, PU.1-dependent, mechanism for developmentally regulated chromatin remodelling and transcription of the c-fms gene. Mol Cell Biol 27 (2007) 878-887. Utilizing PU.1-deficient myeloid progenitors, this study suggests a two-step mechanism by PU.1 controls c-fms gene activation during development. The factor first binds to the c-fms promoter region to maintain its primed status in progenitor cells. It then binds to the enhancer region, together with other factors, to fully activate c-fms expression in differentiated myeloid cells.
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This study demonstrates that IL-7 signaling controls B-cell fate specification through the up-regulation of EBF.
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+ subset of ETPs in the thymus that exhibits weak B-lineage potential. The generation and subsequent differentiation of ETPs was found to require Notch signaling. In contrast, circulating T-cell precursors were still detectable, even in the absence of Notch signaling, suggesting that Notch signals crucial for T-lineage development are required soon after the thymus is seeded.
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+ subset of ETPs in the thymus that exhibits weak B-lineage potential. The generation and subsequent differentiation of ETPs was found to require Notch signaling. In contrast, circulating T-cell precursors were still detectable, even in the absence of Notch signaling, suggesting that Notch signals crucial for T-lineage development are required soon after the thymus is seeded.
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Requirement for Notch1 signals at sequential early stages of intrathymic T cell development
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In contrast to the previously described increased B-cell formation in Notch-knockout mice [43], this study reports that the B-cell potential of ETPs is not augmented under conditions that limit Notch1 activation. It suggests that weak Notch signals are sufficient to suppress B-cell production by thymus seeding cells before reaching the ETP stage and that higher levels are required for the proliferation and differentiation of ETPs.
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Tan J.B., Visan I., Yuan J.S., and Guidos C.J. Requirement for Notch1 signals at sequential early stages of intrathymic T cell development. Nat Immunol 6 (2005) 671-679. In contrast to the previously described increased B-cell formation in Notch-knockout mice [43], this study reports that the B-cell potential of ETPs is not augmented under conditions that limit Notch1 activation. It suggests that weak Notch signals are sufficient to suppress B-cell production by thymus seeding cells before reaching the ETP stage and that higher levels are required for the proliferation and differentiation of ETPs.
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Using clonal switch-culture analyses, this study showed that, for as long as one week after culturing fetal liver progenitors on OP9-DL1 stroma, progeny of some pluripotent progenitors still maintained B-cell potential. This suggests that continuous Notch signaling is required for the maintenance of T-cell development.
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Taghon T.N., David E.S., Zuniga-Pflucker J.C., and Rothenberg E.V. Delayed, asynchronous, and reversible T-lineage specification induced by Notch/Delta signaling. Genes Dev 19 (2005) 965-978. Using clonal switch-culture analyses, this study showed that, for as long as one week after culturing fetal liver progenitors on OP9-DL1 stroma, progeny of some pluripotent progenitors still maintained B-cell potential. This suggests that continuous Notch signaling is required for the maintenance of T-cell development.
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This study shows that expression of the macrophage-associated transcription factors C/EBPα and PU.1 in fully committed pre-T cells converts the cells into functional macrophages or myeloid dendritic cells, respectively. The induced differentiation is inhibited by Notch signaling, indicating a reciprocal antagonism between C/EBPα and PU.1 on one hand and activated Notch on the other.
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Laiosa C.V., Stadtfeld M., Xie H., de Andres-Aguayo L., and Graf T. Reprogramming of committed T cell progenitors to macrophages and dendritic cells by C/EBP alpha and PU.1 transcription factors. Immunity 25 (2006) 731-744. This study shows that expression of the macrophage-associated transcription factors C/EBPα and PU.1 in fully committed pre-T cells converts the cells into functional macrophages or myeloid dendritic cells, respectively. The induced differentiation is inhibited by Notch signaling, indicating a reciprocal antagonism between C/EBPα and PU.1 on one hand and activated Notch on the other.
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Adams, S.L.7
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