Extended Data Fig. 9: The spatiotemporal cellular dynamics and extrinsic cues during liver regeneration.
From: A spatiotemporal atlas of cholestatic injury and repair in mice
a. Average intensity of indicated cell scores for each zonation layer in all Stereo-seq sections (Two-sided wilcoxon rank sum test, Monocyte: p < 2.22e-16; LAM: p < 2.22e-16; Neutrophil: p < 2.22e-16; Cholangiocyte: p = 0.22; Fibroblast: p = 0.97). b. Expression of indicated genes in all Stereo-seq sections at each time point. c. Spatial visualization of the Mki67+ bins in representative Stereo-seq sections. Bins were colored by zonation layer. Scale bar, 500 μm. d. Temporal dynamics of normalized expression of Mki67 in all Stereo-seq sections. e. Expression of Mki67 in hepatocyte from scRNA-seq at each time point during injury and repair (Two-sided wilcoxon rank sum test; At R2, Layer7-9 versus Layer1-2: p = 5.07e-11, Layer7-9 versus Layer3-6: p < 2.22e-16; Layer3-6 versus Layer1-2: p < 2.22e-16; At R7, Layer7-9 versus Layer1-2: p < 2.22e-16, Layer7-9 versus Layer3-6: p = 1.30e-05; Layer3-6 versus Layer1-2: p = 1.08e-13). The range of data in each layer at each time point is presented by grey boxes. f. Average overall, periportal and pericentral ligand-receptor interaction strength for each zonation layer in all Stereo-seq sections at each time point. g. Left: pericentral enriched ligand-receptor interaction strength for each zonation layers in all Stereo-seq sections. Right: spatial visualization of interactions in the left panel for a representative area. Asterisks indicated that interaction distribution was zonal, based on ligand-receptor interactions across nine layers at R2 (Kruskal-Wallis test, q < 0.05). Black line indicated the position of median zonation layer. CV indicated the pericentral region of lobule. h. Average normalized expression of WNT promoting ligands for each zonation layer in all Stereo-seq sections at each time point. i. Expression of WNT promoting ligands in each cell type from scRNA-seq at R2. j. Ppib (red, positive control) and DapB (red, negative control) mRNA ISH co-staining with DAPI on liver sections. The staining was repeated independently two times with similar results. The periportal field of view was shown. Scale bar, 100 μm. k. Expression of indicated ligands in each cell type from scRNA-seq at R2. l. Average module score of TGFb signaling pathways in pericentral (CV Hep), midzonal (MZ Hep), and periportal (PV Hep) hepatocyte from scRNA-seq at D17 and R2. m. Average expression of cell cycle inhibitors in each zone of hepatocyte from scRNA-seq at D17.
