GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE280nnn/GSE280461/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE280461GEOGSEfalseFibroblastic reticular cells drive sympathetic nerve reinnervation to adapt to lymph node expansion induced by tumor cellsLymph nodes (LNs) are peripheral immune organs innervated by sympathetic and sensory nerves. Upon diverse stimuli, LNs undergo substantial structural reorganization and volume expansion. However, the adaptation of innervation to these changes remains poorly understood. In this study, whole-mount 3D imaging revealed that sympathetic nerve fibers, rather than sensory nerves, exhibited significant elongation and increased branching over time during tumor-induced lymph node enlargement (TLNE). Single-nucleus RNA Sequencing (snRNA-seq) analysis demonstrated that throughout TLNE, fibroblastic reticular cells (FRCs) are activatedand engage in neuro-related signaling pathways while secreting substantial amounts of hepatocyte growth factor (HGF). Moreover, the stiffness of the extracellular matrix (ECM) in LNs increased in the context of TLNE, further supporting FRC activation and HGF secretion. The role of HGF in promoting sympathetic nerve fiber outgrowth was confirmed by administering specific HGF inhibitors or using adeno-associated virus (AAV)-mediated HGF silencing. Collectively, HGF secreted by FRCs plays a pivotal role in TLNE, triggering adaptive sympathetic nerve outgrowth and reinnervation within LNs, providing novel insights into neuro-stromal-immune system crosstalk.2026/05/01GSE280461GSM8598182GSM859818324247280461Mus musculus