Somatosensory neurons express specific sets of lincRNAs, and lincRNA CLAP promotes itch sensation in mice

Somatosensory neurons are highly heterogeneous with distinct types of neural cells responding to specific stimuli. However, the distribution and roles of cell‐type‐specific long intergenic noncoding RNAs (lincRNAs) in somatosensory neurons remain largely unexplored. Here, by utilizing droplet‐based single‐cell RNA‐seq (scRNA‐seq) and full‐length Smart‐seq2, we show that lincRNAs, but not coding mRNAs, are enriched in specific types of mouse somatosensory neurons. Profiling of lincRNAs from single neurons located in dorsal root ganglia (DRG) identifies 200 lincRNAs localized in specific types or subtypes of somatosensory neurons. Among them, the conserved cell‐type‐specific lincRNA CLAP associates with pruritus and is abundantly expressed in somatostatin (SST)‐positive neurons. CLAP knockdown reduces histamine‐induced Ca 2+ influx in cultured SST‐positive neurons and in vivo reduces histamine‐induced scratching in mice. In vivo knockdown of CLAP also decreases the expression of neuron‐type‐specific and itch‐related genes in somatosensory neurons, and this partially depends on the RNA binding protein MSI2. Our data reveal a cell‐type‐specific landscape of lincRNAs and a function for CLAP in somatosensory neurons in sensory transmission. Synopsis A single‐cell lincRNA landscape of DRG cells is constructed and hundreds of highly expressed lincRNAs are characterized in distinct types and subtypes of mouse DRG neurons. A highly conserved lincRNA CLAP specifically expressed in somatostatin‐positive neurons regulates histamine‐mediated neuronal activation, acute itch, and type‐specific gene expression. scRNA‐seq reveals that hundreds of lincRNAs are preferentially enriched in the specific type and subtype of somatosensory neurons. Knockdown of CLAP , a conserved and abundant lincRNA in somatostatin‐positive neurons, reduces histamine‐induced neuronal activation and itch sensation. In vivo repression of CLAP reduces neuron type‐specific and itch‐related gene expression, and this partially depends on the RNA binding protein MSI2. Graphical Abstract Single‐cell lincRNA expression characterizes distinct types and subtypes of mouse DRG neurons. The conserved lincRNA CLAP is specifically expressed in somatostatin‐positive neurons and promotes histamine‐mediated neuronal activation, acute itch, and neuron‐type‐specific gene expression.