Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons.
Andrew M BellCharlotte UttingAllen C DickieMateusz W KucharczykRaphaëlle QuilletMaria Gutierrez-MecinasAimi N B RazlanAndrew H CooperYuxuan LanJunichi HachisukaGreg A WeirKirsty BannisterMasahiko WatanabeArtur KaniaMark A HoonIain C MacaulayFranziska DenkAndrew J ToddPublished in: Proceedings of the National Academy of Sciences of the United States of America (2024)
The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies the perception of pain, itch, and skin temperature. Despite its importance, our understanding of this system has been hampered by the considerable functional and molecular diversity of its constituent cells. Here, we use fluorescence-activated cell sorting to isolate ALS neurons belonging to the Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters of ALS neurons (ALS1-5) and document their laminar distribution in the spinal cord using in situ hybridization. We identify three clusters of neurons located predominantly in laminae I-III of the dorsal horn (ALS1-3) and two clusters with cell bodies located in deeper laminae (ALS4 and ALS5). Our findings reveal the transcriptional logic that underlies ALS neuronal diversity in the adult mouse and uncover the molecular identity of two previously identified classes of projection neurons. We also show that these molecular signatures can be used to target groups of ALS neurons using retrograde viral tracing. Overall, our findings provide a valuable resource for studying somatosensory biology and targeting subclasses of ALS neurons.
Keyphrases
- spinal cord
- amyotrophic lateral sclerosis
- neuropathic pain
- single cell
- spinal cord injury
- sars cov
- computed tomography
- genome wide
- single molecule
- transcription factor
- pain management
- oxidative stress
- magnetic resonance imaging
- mesenchymal stem cells
- pulmonary artery
- induced apoptosis
- signaling pathway
- pulmonary hypertension
- working memory
- brain injury
- cell death
- blood brain barrier
- white matter