Innate lymphoid cells (ILCs) play strategic roles in tissue homeostasis and immunity. ILCs arise from lymphoid progenitors undergoing lineage restriction and the development of specialized ILC subsets. We generated "5x polychromILC" transcription factor reporter mice to delineate ILC precursor states by revealing the multifaceted expression of key ILC-associated transcription factors (Id2, Bcl11b, Gata3, RORγt, and RORα) during ILC development in the bone marrow. This approach allowed previously unattained enrichment of rare progenitor subsets and revealed hitherto unappreciated ILC precursor heterogeneity. In vivo and in vitro assays identified precursors with potential to generate all ILC subsets and natural killer (NK) cells, and also permitted discrimination of elusive ILC3 bone marrow antecedents. Single-cell gene expression analysis identified a discrete ILC2-committed population and delineated transition states between early progenitors and a highly heterogeneous ILC1, ILC3, and NK precursor cell cluster. This diversity might facilitate greater lineage potential upon progenitor recruitment to peripheral tissues.

中文翻译：

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多色报告小鼠揭示骨髓中未被重视的先天淋巴细胞祖细胞异质性和难以捉摸的 ILC3 祖细胞。

先天淋巴细胞 (ILC) 在组织稳态和免疫中发挥重要作用。ILC 起源于经历谱系限制和专门 ILC 亚群发展的淋巴祖细胞。我们生成了“5x polychromILC”转录因子报告小鼠，通过揭示骨髓 ILC 发育过程中关键 ILC 相关转录因子（Id2、Bcl11b、Gata3、RORγt 和 RORα）的多方面表达来描绘 ILC 前体状态。这种方法允许以前未实现的稀有祖细胞亚群富集，并揭示了迄今为止未被认可的 ILC 前体异质性。体内和体外测定鉴定了具有产生所有 ILC 亚群和自然杀伤 (NK) 细胞的潜力的前体，并且还允许区分难以捉摸的 ILC3 骨髓前体。单细胞基因表达分析确定了一个离散的 ILC2 承诺群体，并描绘了早期祖细胞与高度异质的 ILC1、ILC3 和 NK 前体细胞簇之间的过渡状态。这种多样性可能有助于在将祖细胞募集到外周组织时产生更大的谱系潜力。