A multi-omic atlas of human autonomic and sensory ganglia implicates cell types in peripheral neuropathies

The human peripheral nervous system (PNS) consists of many ganglia, including sympathetic ganglia (SG) and dorsal root ganglia (DRG), that house the cell bodies of many constituent neuron types and non-neuronal cells of the PNS. However, the molecular and cellular diversity of these human PNS cell types and their implications in human diseases remain elusive. By generating an integrated single-cell multi-omic atlas of human SG and DRG, we provide comprehensive transcriptional and epigenomic landscapes of various cell types in these peripheral ganglia. While the major cell types and their transcriptional and epigenomic features are similar between human SG and DRG, we identify key transcriptional and epigenomic differences between SG and DRG cell types, highlighting the distinct molecular mechanisms underlying their specific functions. Moreover, by mapping the expression and chromatin accessibility of disease-associated genes in human SG and DRG cell types, we identify cellular and molecular mechanisms that may underlie various peripheral neuropathies. This atlas serves as a valuable resource for understanding the intricate cell-type-specific molecules and interactions in the human PNS and their implications in human health and diseases.