Single-cell Transcriptomics Reveals the Heterogeneous Landscape of Innate Lymphoid Cells in Zebrafish

They constitute a major lymphocyte compartment and likely play a prominent role in lower vertebrates, though their precise composition and functions remain poorly characterized. Here, using scRNA-seq, we identify a broad spectrum of distinct ILC subsets, including both conventional subsets resembling their mammalian counterparts and unconventional ILC-like populations with unique features and distinct tissue distributions.

We demonstrate that the complete ILC repertoire emerges early in development, independent of hematopoietic stem cells (HSCs), yet is maintained into adulthood via an HSC-dependent mechanism. Our work defines the landscape and ontogeny of zebrafish ILCs, revealing their underappreciated diversity and providing key insights into vertebrate innate immunity evolution.