Blood feeding triggers the terminal differentiation of precursor cells in tick salivary glands.

Ticks transmit a wide range of pathogens to humans. During blood feeding, they inject salivary proteins that suppress host immune responses, enabling prolonged feeding and pathogen transmission. A hallmark of this process is the dynamic reprogramming of salivary gene expression, known as the sialome switch. Here, we describe a previously unrecognized cellular mechanism underlying this phenomenon in two medically important tick species. Using integrated multi-omics and imaging approaches, we identified a conserved population of undifferentiated salivary gland precursor cells in unfed ticks. Upon host attachment, these precursors undergo terminal differentiation into specialized secretory subtypes through a conserved transcriptional and signaling framework that drives salivary gland activation and maturation. Unlike other blood-feeding arthropods, tick salivary glands dynamically remodel in response to host contact, producing saliva with a shifting composition. This study suggests the cellular basis of adult female tick salivary gland maturation and offers targets to disrupt feeding and pathogen transmission.