A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation [scRNA-seq]

Compared to the well-established functions of sympathetic innervation, the role of sensory afferents in adipose tissues remains less understood. Recent work revealed the anatomical and physiological significance of adipose sensory innervation; however, its molecular underpinning remains unclear. Here, using organ-targeted single-cell RNA sequencing, we identified the mechanoreceptor PIEZO2 as one of the most prevalent receptors in fat-innervating dorsal root ganglia (DRG) neurons. Selective PIEZO2 deletion in fat-innervating neurons led to molecular alternations in adipose tissue similar to DRG ablation. Conversely, a gain-of-function PIEZO2 mutant shifted the adipose phenotypes in the opposite direction. These results indicate that PIEZO2 plays a major role in the sensory regulation of adipose tissues. This discovery opens new avenues for exploring mechanosensation in organs not traditionally considered mechanically active, such as the adipose tissues, and therefore sheds light on the broader significance of mechanosensation in regulating organ function and homeostasis. Overall design: To identify the sensory neuron cell types innervating adipose tissues, DRGs were dissected from male mice that received CTB488 injections into iWAT and CTB647 injections into eWAT. DRGs from spinal levels T10 to L6 were collected, dissociated, and subjected to FACS sorting to isolate 488+, 647+, and double-negative populations. Sorted cells were processed using the 10x Genomics platform, with samples pooled from 16 mice.