Fig. 4: DART-FISH mapping of a diseased human kidney.
From: Mapping human tissues with highly multiplexed RNA in situ hybridization
a Applying DART-FISH to a 4.9x3.8mm2 section from the cortex of the human kidney (adapted from BioRender). The nephron schematics shows the expected epithelial subclasses in the section101. b The spatial expression of key marker genes for the cortical segments: EMCN: glomerular capillary endothelial cells (EC-GC), NPHS2: podocytes (POD), LRP2: proximal tubules (PT), SLC12A1: cortical thick ascending limbs (C-TAL), SLC12A3: distal convoluted tubules (DCT), AQP2: cortical principal cells of the collecting duct (C-PC). c UMAP of all annotated subclasses. PEC: parietal epithelial cells, aPT: altered proximal tubules, DTL: descending thin limbs, aTAL: altered thick ascending limbs, DCT: distal convoluted tubules, CNT: connecting tubules, C-IC-A: cortical intercalated cell type A, IC-B: intercalated cell type B, EC-PTC: peritubular capillary endothelial cell, MC: mesangial cell, REN: renin-positive juxtaglomerular granular cell, VSMC: vascular smooth muscle cell, VSMC/P: vascular smooth muscle cell/pericyte, FIB: fibroblast, MYOF: Myofibroblast, MAC-M2: M2 macrophage, IMM-Lym: lymphoid cell, IMM-Myl: myeloid cell. d Dot plot of marker gene expression for the annotated subclasses. e An example of a glomerulus with part of the juxtaglomerular apparatus. (top) cells colored by the annotated subclass, (bottom) marker genes corresponding to the subclasses. Each dot represents one rolony. Dashed line delineates the boundary of the renal corpuscle. f Example of a medullary ray with a bundle of TALs, PT-S3, and collecting ducts. Note that for clarity, some cell types, i.e., aPT, FIB, aTAL1 and MYOF are plotted (top) but their corresponding marker genes are omitted (bottom). g Example of a pathological niche with inflammation, a sclerosed glomerulus and altered proximal tubule cells adjacent to a more normal glomerulus (top). The same area on an H&E-stained parallel section from the same tissue block confirms the decellularization and inflammation observed in DART-FISH. The black arrow points to the sclerotic glomerulus. h Example of a pathological niche composed of aTAL1 cells and myofibroblasts. Red arrows point toward densities of MYOF and aTAL1 cells.
