Single-Cell Gene Expression Analyses Reveal Heterogeneous Responsiveness of Fetal Innate Lymphoid Progenitors to Notch Signaling
Single-Cell Gene Expression Analyses Reveal Heterogeneous Responsiveness of Fetal Innate Lymphoid Progenitors to Notch Signaling
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DOI：
10.1016/j.celrep.2016.01.015
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发表时间：
2016-02-16
期刊：
影响因子：
8.8
通讯作者：
Golub, Rachel
中科院分区：
文献类型：
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作者：
Chea, Sylvestre;Schmutz, Sandrine;Golub, Rachel
T细胞和先天性淋巴样细胞（ILC）在某些方面有着共同的发育程序。然而，尽管Notch信号传导对于T细胞发育是严格需要的，但它对于胎儿ILC发育是不必要的。在共同淋巴祖细胞阶段，Notch信号传导的组成性激活驱动T细胞发育并通过阻止Id 2表达来消除ILC发育。通过结合单细胞转录组学和克隆培养策略，我们表征了两个异质性α（4）β（7）表达淋巴祖细胞区室。α LP 1（Flt 3（+））仍保留T细胞潜能并包含整体ILC祖细胞，而α LP 2（Flt 3（-））由向不同ILC谱系引发的ILC前体组成。只有一部分α-LP 2前体对它们增殖所需的Notch信号传导敏感。我们的研究确定，在一个精致的方式，ILC发展的过渡阶段的多样性，他们的转录签名，和他们的差异依赖于Notch信号。
T and innate lymphoid cells (ILCs) share some aspects of their developmental programs. However, although Notch signaling is strictly required for T cell development, it is dispensable for fetal ILC development. Constitutive activation of Notch signaling, at the common lymphoid progenitor stage, drives T cell development and abrogates ILC development by preventing Id2 expression. By combining single-cell transcriptomics and clonal culture strategies, we characterize two heterogeneous alpha(4)beta(7)-expressing lymphoid progenitor compartments. alpha LP1 (Flt3(+)) still retains T cell potential and comprises the global ILC progenitor, while alpha LP2 (Flt3(-)) consists of ILC precursors that are primed toward the different ILC lineages. Only a subset of alpha LP2 precursors is sensitive to Notch signaling required for their proliferation. Our study identifies, in a refined manner, the diversity of transitional stages of ILC development, their transcriptional signatures, and their differential dependence on Notch signaling.