Regenerative epithelial spike cells instruct immune niche homeostasis in zebrafish fin epidermis

Abstract

Epithelia comprise diverse specialized epithelial cells that interact with immune cells, yet how these interactions sustain immune cell pools remain poorly understood. Here, we integrated single-cell RNA sequencing (scRNA-seq) analysis with transgenic assays in zebrafish and discovered a previously unrecognized epithelial population marked by advillin (avil). We identified epithelial cells exhibiting unique morphology and localization, characterized by an apical spike projecting outward from the body - which we term spike cells. These cells exhibit features reminiscent of mammalian tuft cells. Notably, avil+ spike cells exhibit close spatial association with a subset of mpeg1+ immune cells. Following fin amputation, spike cells are replenished de novo from precursors and undergo dynamic changes in density, morphology, and orientation, and their regeneration depends on Alk signaling. Moreover, spike cells dynamically interact with mpeg1+ immune cells to maintain the immune cell population. Together, our findings identify a unique epithelial population in zebrafish fins and define their roles in maintaining immune cell niche dynamics.