Cell · 2026
Molecular architecture of human dermal sleeping nociceptors.
СтатьяНазвание и аннотация: Перевод в очереди
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Körner Jannis, Howard Derek, Solinski Hans Jürgen, Mancilla Moreno Marisol, Haag Natja, Fiebig Andrea, Maxion Anna, Bhuiyan Shamsuddin A, Toklucu Idil, Bott Raya A, Sankaranarayanan Ishwarya, Tavares-Ferreira Diana, Shiers Stephanie, Inturi Nikhil N, Eberhardt Esther, Ernst Lisa, Bonaguro Lorenzo, Schulte-Schrepping Jonas, Beyer Marc D, Stiehl Thomas, Renthal William, Kurth Ingo, Tigerholm Jenny, Serra Jordi, Price Theodore J, Schmelz Martin, Namer Barbara, Tripathy Shreejoy, Lampert Angelika
Аннотация
Human dermal sleeping nociceptors display ongoing activity in neuropathic pain, affecting 10% of the population. Despite advances in rodents, a molecular marker for these mechano-insensitive C-fibers (CMis) in human skin remains elusive, preventing targeted therapy. Using a Patch-seq approach, we combined single-cell transcriptomics, following electrophysiological characterization, with single-nucleus and spatial transcriptomics from pigs and integrated our findings with cross-species and human transcriptomic data. We functionally identified CMis in pig sensory neurons with patch clamp, using adapted protocols from human microneurography. We identified oncostatin M receptor (OSMR) and somatostatin (SST) as marker genes for CMis. Following dermal injection in healthy human volunteers, oncostatin M, the ligand of OSMR, exclusively modulates CMis. Our findings characterize the molecular architecture of human dermal sleeping nociceptors, providing a framework for mechanistic insight into neuropathic pain and potential therapeutic strategies.