Fig. 3: Rare cell subpopulations associated with proteinuria identified using UDA-seq.
a, A violin plot displaying the distribution of positive proteinuria signature scores across different cell types. Box plots show the interquartile range with the median marked. The whiskers extend up to 1.5 times the interquartile range, and the outliers are not displayed. b. Left: the anatomical structure of the glomerulus, with arrows indicating a podocyte and EC-GC. Right: UMAP embedding, colored by positive proteinuria signature score, highlighting the enrichment of the proteinuria signature in the podocyte. c, A heatmap providing a visual representation of the enrichment of cells related to proteinuria positivity or negativity across different donors. The colors in the heatmap correspond to the enrichment scores. Donors were categorized into three groups: healthy, those with 24 h urinary protein levels ≥3.5 g and those with levels <3.5 g. d, A box plot depicting donors’ positive proteinuria signature scores across the control (n = 10), low proteinuria (n = 19) and high proteinuria (n = 6) group. The box plots show the interquartile range with the median marked. The whiskers extend up to 1.5 times the interquartile range. P values were calculated using the two-sided t test. *Bonferroni-adjusted P < 0.05. **Bonferroni-adjusted P < 0.01. e. Podocyte reclustering, revealing six subclusters. f, UMAP embedding, colored to indicate cells positively related to proteinuria. g, A Volcano plot showing marker genes of subcluster 1 for podocytes. P values were calculated by the two-sided Wilcoxon rank sum test. The vertical dashed lines represented −1 or 1 log2FC value, the horizontal dashed line represented p-value = 0.05. h, The key eRegulon identified by SCENIC+. Bold and enlarged gene symbols represent transcription factors (TFs), squares represent peak regions and gene symbols at the graph’s edges represent regulated genes. i, A heatmap illustrating the differential cell–cell communication strength of proteinuria donors compared with healthy control donors. j, A bar plot illustrating that the podocyte-to-EC-GC communication changes between donors with proteinuria and healthy control donors in the fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), neuregulins (NRG) and platelet-derived growth factor (PDGF) signaling pathway. The FGF signaling pathway exhibits an increase in proteinuria donors. Panel b was created using BioRender.com. Full names for all abbreviations of cell types in panels a,b,i can be found in the Methods.
