GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE284nnn/GSE284696/primaryOK200TranscriptomicsMusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284696GEOGSEfalseObesity-mediated intratumoral innervation increases pancreatic cancer tumorigenesis [scRNA-seq]The incidence of pancreatic ductal adenocarcinoma (PDAC) is on the rise, and host factors like obesity increase risk by 60% and mortality by two-fold; however, the mechanisms that drive obesity-associated tumorigenesis are poorly understood. Here, we showed that obesity-mediated pancreatic steatosis was associated with a higher level of neo-innervation in PDAC. Neo-innervation mostly comprised sympathetic neurons that released catecholamines, which ligated the adrenergic receptor on both tumor and immune cells, subsequently activating a downstream signaling cascade that led to a pro-tumorigenic type 2 immune microenvironment accelerating tumorigenesis. Further, we identified NgCAM-related cell adhesion molecule (NrCAM) and nerve growth factor (NGF) as major mediators secreted by adipocytes that drove neurogenesis. Targeting neuro-adrenergic signaling by nerve ablation or pharmacologic approaches abolished obesity-related tumor progression. Overall, this study advances our understanding of the fundamental biology underpinning obesity-mediated neo-innervation and its causal link to exacerbating PDAC development, providing new avenues for therapeutic intervention.2026/05/08GSE284696GSM8690715GSM8690726GSM8690725GSM8690714GSM8690717GSM8690716GSM8690722GSM8690721GSM8690724GSM8690723GSM8690719GSM8690718GSM869072035134284696Mus