The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor. Mus musculus

Innate lymphoid cells (ILCs) are recently identified lymphocytes that limit infection and promote tissue repair at mucosal surfaces. However, the pathways underlying ILC development remain unclear. Here we show that the transcription factor NFIL3 directs the development of a committed bone marrow precursor that differentiates into all known ILC lineages. NFIL3 was required in the common lymphoid progenitor (CLP), and was essential for the differentiation of CLP, a bone marrow cell population that gives rise to all known ILC lineages. Clonal differentiation studies revealed that CXCR6+ cells within the CLP population differentiate into all ILC lineages but not T- and B-cells. We further show that NFIL3 governs ILC development by directly regulating expression of the transcription factor TOX. These findings establish that NFIL3 directs the differentiation of a committed ILC precursor that gives rise to all ILC lineages and provide insight into the defining role of NFIL3 in ILC development. This experiment is to compare gene expression profiles between wild-type and Nfil3-/- common lymphoid progenitor (CLP) cells to identify genes regulated by NFIL3. Overall design: There are 6 samples in this experiment, including 3 biological replicates for wild-type CLPs and 3 biological replicates for Nfil3-/- CLPs. All mice used are on the C57BL/6 background.

固有淋巴样细胞（Innate lymphoid cells, ILCs）是近年被鉴定出的淋巴细胞，可在黏膜表面限制感染并促进组织修复。然而，ILC发育的潜在调控通路仍不明确。本研究证实，转录因子NFIL3可调控一类定向分化的骨髓祖细胞的发育，该祖细胞可分化为所有已发现的ILC谱系。转录因子NFIL3在常见淋巴样祖细胞（common lymphoid progenitor, CLP）中发挥必需作用，且对于CLP的分化至关重要——CLP是一类可产生所有已知ILC谱系的骨髓细胞群。克隆分化实验显示，CLP群体中的CXCR6阳性细胞可分化为所有ILC谱系，但无法分化为T细胞与B细胞。本研究进一步证实，NFIL3可通过直接调控转录因子TOX的表达来调控ILC发育。上述发现确立了NFIL3可定向分化出可产生所有ILC谱系的定向ILC祖细胞，并为理解NFIL3在ILC发育中的核心作用提供了新的研究视角。本实验旨在对比野生型与Nfil3基因敲除的常见淋巴样祖细胞（CLP）的基因表达谱，以鉴定受NFIL3调控的基因。实验整体设计：本实验共包含6个样本，其中野生型CLP与Nfil3-/- CLP各设置3个生物学重复。所有实验小鼠均采用C57BL/6品系背景。