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Omics · study · 2026

Fibroblastic reticular cells drive sympathetic nerve reinnervation to adapt to lymph node expansion induced by tumor cells

Listed in NCBI GEO

Lymph nodes (LNs) are peripheral immune organs innervated by sympathetic and sensory nerves.

Description

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).

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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.

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Life Sciences
Inferred from text
Cancer 65% · Imaging 75% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 12 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE28046113 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:imagingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:single-cell-rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title