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首页> 外文期刊>The British journal of psychiatry : >Multi-transcription factor reporter mice delineate early precursors to the ILC and LTi lineages
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Multi-transcription factor reporter mice delineate early precursors to the ILC and LTi lineages

机译:多转录因子报告小鼠将早期前体描绘给ILC和Lti谱系

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Transcription factor (TF) reporter mice have proved integral to the characterization of murine innate lymphoid cell (ILC) development and function. Here, we implemented a CRISPR/Cas9-generated combinatorial reporter approach for the simultaneous resolution of several key TFs throughout ILC development in both the fetal liver and adult bone marrow. We demonstrate that the Tcf7-expressing early innate lymphoid precursor (EILP) and the common helper ILC precursor (CHILP) both contain a heterogeneous mixture of specified ILC and lymphoid tissue inducer (LTi) precursors with restricted lineage potential rather than a shared precursor. Moreover, the earliest specified precursor to the LTi lineage was identified upstream of these populations, before Tcf7 expression. These findings match dynamic changes in chromatin accessibility associated with the expression of key TFs (i.e., GATA3 and ROR gamma(t)), highlighting the distinct origins of ILC and LTi lineages at the epigenetic and functional levels, and provide a revised map for ILC development.
机译:转录因子(TF)报告小鼠已被证明是小鼠固有淋巴细胞(ILC)发育和功能表征的组成部分。在这里,我们实施了一种CRISPR/Cas9生成的组合报告方法,用于同时解析胎儿肝脏和成人骨髓中ILC发育过程中的几个关键TF。我们证明,表达Tcf7的早期先天性淋巴前体(EILP)和常见辅助性ILC前体(CHILP)均含有特定ILC和淋巴组织诱导物(LTi)前体的异质性混合物,具有有限的谱系潜能,而不是共同的前体。此外,在Tcf7表达之前,在这些群体的上游发现了LTi谱系最早的特定前体。这些发现与关键TFs(即GATA3和ROR伽马(t))表达相关的染色质可及性的动态变化相匹配,突出了ILC和LTi谱系在表观遗传学和功能水平上的不同起源,并为ILC的发展提供了一个修订图。

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