Notch target Hes5 ensures appropriate Notch induced T- versus B-cell choices in the thymus
Notch target Hes5 ensures appropriate Notch induced T- versus B-cell choices in the thymus
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DOI：
10.1182/blood-2007-03-079855
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发表时间：
2008-03-01
期刊：
影响因子：
20.3
通讯作者：
Bernstein, Irwin D.
中科院分区：
文献类型：
--
作者：
Varnum-Finney, Barbara;Dallas, Mari H.;Bernstein, Irwin D.
Notch信号通过诱导t细胞承诺和抑制b细胞选择在胸腺中建立边界。在这里，我们发现与野生型小鼠相比，Notch靶Hes5缺失小鼠胸腺中b细胞前体的产生显著增加1.6倍。我们进一步发现，增加纯化的固定化Notch配体（δ (1ext-IgG)）密度的骨髓源祖细胞培养诱导Notch靶点Hes1和Hes5的表达增加，尽管Hes5缺失的祖细胞对高密度配体有适当的反应，但它们对中、低密度的配体有误读。总之，我们的研究结果表明，为了确保胸腺对诱导Notch信号的低阈值做出适当的反应，需要诱导额外的靶标Hes5。
Notch signaling establishes boundaries in the thymus by inducing T-cell commitment and inhibiting a B-cell choice. Here, we show a significant 1.6-fold increased generation of B-cell precursors in thymuses from mice deficient for Notch target Hes5 compared with wild-type littermates. We further show that culture of bone marrow-derived progenitors with increasing densities of purified immobilized Notch ligand (Delta(1ext-IgG)) induced increased expression of Notch targets Hes1 and Hes5, and that although Hes5- deficient progenitors responded appropriately to high densities of ligand, they misread intermediate and low densities. Together, our results suggest that to ensure an appropriate outcome in the thymus in response to a lower threshold of induced Notch signaling, induction of the additional target Hes5 is required.