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A detailed molecular profile of pancreatic sensory neurons could provide insights into their role in health and disease, particularly in pancreatic ductal adenocarcinoma (PDAC), where neural remodeling influences tumor progression and pain signaling. Wild\u2010type and PDAC mice were injected with the retrotracer Fast Blue into pancreatic or cancerous tissue. Dorsal root ganglia were dissociated, and Fast Blue\u2010positive sensory neurons were isolated, lysed, and analyzed using single\u2010cell RNA sequencing. Data were validated using immunofluorescence, organoid cultures and qPCR. We performed transcriptomic profiling of sensory neurons innervating the pancreatic head and tail under normal and cancer conditions. Our analysis identified neurofilament\u2010containing neurons as the predominant sensory subtype in both contexts, while non\u2010peptidergic neurons were underrepresented in tumor\u2010associated innervation. Differential gene expression analysis revealed a unique subset of genes upregulated in sensory neurons innervating pancreatic tumors, many linked to mitochondrial activity. Further validation also revealed the presence of transcripts transferred via extracellular vesicles (including the Pdx1\u2010CreERT2 transgene from the KPC mouse model), suggesting a novel mechanism of tumor\u2013neuron interaction. Our findings provide a detailed characterization of pancreatic and pancreatic ductal adenocarcinoma sensory innervation. We identified tumor\u2010derived RNA within sensory neurons in the PDAC mouse model, suggesting an extracellular vesicle\u2013mediated RNA transfer mechanism that may remodel sensory signaling and open new prospects for diagnostic and therapeutic innovation in PDAC.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"box\" position=\"anchor\">\n                      <jats:caption>\n                        <jats:title>Impact statement<\/jats:title>\n                      <\/jats:caption>\n                      <jats:p>Transcriptomic profiling of pancreatic sensory neurons reveals shifts in neuronal populations, tumor\u2010specific mitochondrial gene upregulation, and potential extracellular vesicle\u2013mediated transcript transfer. Circulating tumor transcripts in KPC mice provide a reference for pancreatic innervation, tumor\u2013nerve interactions, and therapeutic targets.<\/jats:p>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70233","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:03:13Z","timestamp":1773824593000},"page":"1726-1741","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deciphering transcriptional plasticity in pancreatic ductal adenocarcinoma reveals alterations in sensory neuron innervation"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6692-6573","authenticated-orcid":false,"given":"Elena","family":"Genova","sequence":"first","affiliation":[{"name":"Institute for Maternal and Child Health\u2010 IRCCS \u201cBurlo Garofolo\u201d  Trieste 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