In an era where the established lines between cell identities are blurred by intra-lineage plasticity, distinguishing between stable and transitional states becomes imperative. This challenge is particularly pronounced within the Group 1 ILC lineage, where the similarity and plasticity between NK cells and ILC1s obscure their classification and the assignment of their unique contributions to immune regulation. This study exploits the unique property of Asialo-GM1 (AsGM1), a membrane lipid associated with cytotoxic attributes absent in ILC1s, as a definitive criterion to distinguish between these cells. By prioritizing cytotoxic potential as the cardinal differentiator, our strategic use of the AsGM1 signature achieved precise delineation of NK cells and ILC1s across tissues, validated by RNA-seq analysis. This capability extends beyond steady-state classifications, adeptly capturing the binary classification of NK cells and ILC1s during acute liver injury. By leveraging two established models of NK-to-ILC1 plasticity driven by TGFβ and Toxoplasma gondii, we demonstrate the stability of the AsGM1 signature, which sharply contrasts with the loss of Eomes. This signature identified a spectrum of known and novel NK cell derivatives, ILC1-like entities, that bridge traditional binary classifications in aging and infection. The early detection of the AsGM1 signature at the immature NK (iNK) stage, preceding Eomes, and its stability, unaffected by transcriptional reprogramming that typically alters Eomes, position AsGM1 as a unique, site-agnostic marker for fate mapping NK-to-ILC1 plasticity. This provides a powerful tool to explore the expanding heterogeneity within the Group 1 ILC landscape, effectively transcending the ambiguity inherent to the NK-to-ILC1 continuum.

中文翻译：

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膜脂质特征揭示了 1 类 ILC 的动态景观

在细胞身份之间的既定界限因谱系内可塑性而变得模糊的时代，区分稳定状态和过渡状态变得势在必行。这一挑战在第 1 组 ILC 谱系中尤为明显，其中 NK 细胞和 ILC1 之间的相似性和可塑性掩盖了它们的分类以及它们对免疫调节的独特贡献的分配。这项研究利用了 Asialo-GM1 (AsGM1) 的独特特性，这是一种与 ILC1 中不存在的细胞毒性属性相关的膜脂，作为区分这些细胞的明确标准。通过优先考虑细胞毒性潜力作为主要区别因素，我们对 AsGM1 特征的战略性使用实现了跨组织的 NK 细胞和 ILC1 的精确描绘，并通过 RNA-seq 分析进行了验证。这种能力超越了稳态分类，能够熟练地捕获急性肝损伤期间 NK 细胞和 ILC1 的二元分类。通过利用由 TGFβ 和弓形虫驱动的两个已建立的 NK 至 ILC1 可塑性模型，我们证明了 AsGM1 特征的稳定性，这与 Eomes 的丢失形成鲜明对比。该特征识别了一系列已知的和新型的 NK 细胞衍生物，即 ILC1 样实体，它们连接了衰老和感染的传统二元分类。在 Eome 之前的未成熟 NK (iNK) 阶段早期检测到 AsGM1 特征，其稳定性不受通常会改变 Eome 的转录重编程的影响，将 AsGM1 定位为独特的、位点不可知的标记，用于 NK 到 ILC1 的命运图谱可塑性。这为探索第 1 组 ILC 景观中不断扩大的异质性提供了一个强大的工具，有效地超越了 NK 到 ILC1 连续体固有的模糊性。