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Spatial and Single Cell Mapping of Human Lymph Node Disease

ABSTRACT: To determine the cellular and molecular basis of Castleman Disease (CD), we analyze the spatial proteome of spatial proteome and transcriptome of 22 cases of Unicentric CD, idiopathic Multicentric CD, HHV8-associated MCD, and reactive lymph nodes. CD shows increased stromal cells that form unique microenvironments. Interaction of activated follicular dendritic cell (FDC) cytoplasmic meshworks with mantle-zone B cells is associated with B-cell activation and differentiation. CXCL13+ FDCs, PDGFRA+ T-zone reticular cells (TRC), and ACTA2-positive perivascular reticular cells (PRC) were the predominant source of increased VEGF expression and IL-6 signaling. MCD is characterized by increased TRC while UCD shows increased B-reticular cells (BRC). VEGF expression by FDCs is associated with peri-follicular neovascularization. FDC, TRC and PRC of CD activates JAK-STAT, TGFβ, and MAPK pathways via specific ligand-receptor interactions. Here, we show that stromal-cell activation and associated B-cell activation and differentiation, neovascularization and stromal remodeling underlie CD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE296614 | GEO | 2025/05/09

REPOSITORIES: GEO

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