Single-cell analysis defines the divergence between the innate lymphoid cell lineage and lymphoid tissue-inducer cell lineage.

Single-cell analysis defines the divergence between the innate lymphoid cell lineage and lymphoid tissue-inducer cell lineage.
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DOI:
10.1038/ni.3344
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发表时间:
2016-03
期刊:
影响因子:
30.5
通讯作者:
Golub R
Golub R
中科院分区:
医学1区
文献类型:
--
作者:
Ishizuka IE;Chea S;Gudjonson H;Constantinides MG;Dinner AR;Bendelac A;Golub R

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先天性淋巴样细胞(ILC)和淋巴样组织诱导(LTi)细胞之间的确切谱系关系知之甚少。使用100个淋巴样基因和胎肝前体细胞的单细胞培养物的单细胞多重转录分析,我们确定了这些谱系的共同近端前体,并表明其分叉标记的转录因子PLZF和TCF 1的差异诱导。收购个别ILC亚组特异性效应程序启动后,在共同的ILC前体阶段,混合ILC1,ILC2和ILC3转录模式的瞬时表达,而相反,LTi细胞的发展没有经过多系引发。这些发现为ILC和LTi细胞谱系分化的不同机制提供了见解,并建立了其发展的高分辨率蓝图。
The precise lineage relationship between innate lymphoid cells (ILC) and lymphoid tissue inducer (LTi) cells is poorly understood. Using single-cell multiplex transcriptional analysis of 100 lymphoid genes and single-cell cultures of fetal liver precursor cells, we identified the common proximal precursor to these lineages and showed that its bifurcation was marked by the differential induction of the transcription factors PLZF and TCF1. Acquisition of individual ILC subset-specific effector programs was initiated later, at the common ILC precursor stage, by transient expression of mixed ILC1, ILC2 and ILC3 transcriptional patterns whereas, in contrast, LTi cell development did not go through multilineage priming. These findings provide insights into divergent mechanisms of ILC and LTi cell lineage differentiation and establish a high-resolution blueprint of their development.