A Reference Atlas of the Human Dorsal Root Ganglion

Area of Science:

• Neuroscience
• Genomics
• Cell Biology

Background:

• Dorsal root ganglia (DRG) neurons are crucial for somatosensory perception.
• DRG neuron damage causes chronic pain and sensory loss.
• Human DRG cellular landscape is less understood compared to mice.

Purpose of the Study:

• To construct a comprehensive reference cell atlas of the human DRG.
• To resolve neuronal and non-neuronal cell subtypes within the human DRG.
• To compare human and mouse DRG cell characteristics and function.

Main Methods:

• Single-cell and single-nucleus transcriptomic profiling of 126 human DRG donors.
• Cross-species integration of transcriptomic data.
• Spatial transcriptomics and microneurography for functional comparisons.

Main Results:

• Resolved 22 human DRG neuronal subtypes (including novel ones) and 10 non-neuronal cell types.
• Human DRG somata are larger than mouse counterparts across all cell types.
• Human A-fiber conduction velocity is faster, suggesting enhanced rapid mechanical detection.

Conclusions:

• The human DRG cell atlas is a valuable resource for understanding peripheral nervous system function.
• Findings provide a foundation for identifying new therapeutic targets for chronic pain.
• Differences in human vs. mouse DRG suggest species-specific sensory processing.