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Hematopoietic progenitors recovered from PU.1-null mutant embryos do not express the lymphoid cytokine receptor gene IL-7Rα. Both PU.1 and IL-7Rα transgenes rescue B-lineage differentiation, which is normally abrogated in these mutants, PU.1 being more effective in this regard than IL-7Rα. Chromatin immunoprecipitation (ChIP) assays revealed that PU.1 binds directly to the IL-7Rα promoter. It therefore appears that PU.1 promotes early B-lineage development in large part by facilitating IL-7 signal transduction
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Inspired by the approach of [12], this paper uses powerful single-cell gene expression analyses to prove that individual cells of the CLP and CMP classes are generally lymphoid- or myeloid-restricted in their gene expression profiles, respectively. The authors also show that individual cells of the CLP and CMP classes simultaneously express sets of genes that are normally associated with mutually exclusive developmental fates in their descendants, albeit at levels approximately an order of magnitude below those characteristic of legitimate expression in committed cell types. CLPs coexpress genes that are both T- and B-cell specific, and CMPs coexpress genes that are both myeloid- and erythroid-specific. However, although HSCs promiscuously express a broad spectrum of hematopoietic lineage genes, they are largely devoid of lymphoid expression, perhaps reflecting the late emergence of lymphopoiesis in evolution
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••] are capable of differentiating into T, B, or NK cells, although in each case repression as well as activation of genes is seen with particular cell fates. This body of work emphasizes the regulatory instability of the intermediate states between hematopoietic stem cells and committed lymphoid precursors
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••] are capable of differentiating into T, B, or NK cells, although in each case repression as well as activation of genes is seen with particular cell fates. This body of work emphasizes the regulatory instability of the intermediate states between hematopoietic stem cells and committed lymphoid precursors.
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••,29]. The definition of the developmental window for PU.1 effects here correlates with in vivo regulation of PU.1 in normal pro-T cells, and links the perturbation to in vivo developmental plasticity. The effects of PU.1 misexpression on the pattern of gene expression in a pro-T-like cell line are shown to be governed by bistable switch-like behavior that implicates additional network functions in the response
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••,29]. The definition of the developmental window for PU.1 effects here correlates with in vivo regulation of PU.1 in normal pro-T cells, and links the perturbation to in vivo developmental plasticity. The effects of PU.1 misexpression on the pattern of gene expression in a pro-T-like cell line are shown to be governed by bistable switch-like behavior that implicates additional network functions in the response.
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••]. Here, Spi-B is also shown to be expressed normally in the plasmacytoid class of DCs, and its overexpression enhances the generation of these cells from hematopoietic precursors in a permissive culture system. These observations strengthen the link between the normal expression of Spi-B and PU.1, which continues through the early stages of T-cell development, and the ability of these early T-cell precursors to differentiate along the DC pathway.
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