Fig. 5: Microdissection reveals transcriptional differences between internodular and nodular tumor areas that correspond to distinct MBEN cell stages.

a Heatmap showing differential gene expression between internodular (red column) and nodular (blue column) MBEN compartments. b, c TMEM108, a marker of the internodular compartment, is mainly expressed in early CGNP-like cells. Feature plot on the left depicting gene expression in the snRNA-seq dataset. Boxplot on the right showing expression (measured in batch-effect adjusted RPKM) in microdissected MBEN tissue (limma statistical method p-val = 0.02 with adjustment for multiple genes and tumor samples batch effect) inspected in n = 13 biologically independent samples. d, e TRIM9, a marker of the nodular compartment, is mainly expressed in later stages of MBEN development. Feature plot on the left depicting gene expression in the snRNA-seq dataset. Box plot on the right showing expression in microdissected MBEN tissue (limma statistical method p-val: 0.03 with adjustment for multiple genes and tumor samples batch effect) inspected in n = 13 biologically independent samples. f Mapping of the expression signatures of microdissected internodular and nodular histological compartments to the different snRNA-seq clusters via Gene set variance analysis (GSVA) shows distinct transcriptional similarities between differentiated cells and the nodular compartment, and early-CGNP like cells with the internodular areas. b, c The center line, box limits, whiskers, and points indicate the median, upper/lower quartiles, 1.5× interquartile range and outliers, respectively. Source data are provided as a Source Data file.