The transcription factor NFIL3 drives innate lymphoid cell specification from lymphoid progenitors [RNA-seq - Tox]

Helper innate lymphoid cells (ILC) play important functions in immunity and tissue homeostasis, but their development remains poorly understood. In this study, we identified NFIL3 as the earliest known requirement during ILC development. Forced expression of NFIL3 in mouse lymphoid progenitors in vitro triggered the staged expression of downstream transcription factors including Tcf7, Gata3, Zbtb16 and Id2 that are implicated in ILC development. Thus, NFIL3 resides at the apex of a hierarchy of transcription factors important for innate lymphocyte development, and is necessary and sufficient to impose the innate lymphoid cell fate. Overall design: Bulk RNA-seq comparing ILC precursors generated by forcibly expressing TOX or control GFP in lymphoid precursors

辅助固有淋巴样细胞（Helper innate lymphoid cells, ILC）在免疫应答与组织稳态中发挥重要功能，但其发育机制仍有待深入阐明。本研究鉴定出NFIL3是目前已知的固有淋巴样细胞发育过程中最早的必需调控因子。在体外对小鼠淋巴祖细胞强制过表达NFIL3，可触发下游与固有淋巴样细胞发育相关的转录因子（包括Tcf7、Gata3、Zbtb16及Id2）的阶段性表达。由此可见，NFIL3位于调控固有淋巴细胞发育的转录因子级联网络的顶端，且足以并必需诱导固有淋巴样细胞的细胞命运特化。实验整体设计：通过在淋巴祖细胞中强制过表达TOX或对照绿色荧光蛋白（GFP）以生成固有淋巴样细胞前体，随后进行批量RNA测序（Bulk RNA-seq）比较两组样本的转录组差异。