Towards a Glomerulus Nanoscale Spatial Atlas

Abstract

The glomerulus is the basic filtration apparatus of the kidney, where thousands of the capillary-rich structures function to remove waste products from the blood stream while retaining macromolecules and blood cells. This thesis develops the groundwork for establishing a Glomerular Nanoscale Spatial Atlas (GNSA). The GNSA will be the first resource of its kind, which will include a detailed annotated collection of high spatial resolution (~50 nm) three-dimensional (3D) reconstructions of glomeruli obtained from healthy, aged, and diseased kidney tissues in mouse and human. Data from a single analyzed glomerulus of a healthy female mouse was used to develop this pipeline and is presented here. Fundamental glomerular structures such as the Bowman's capsule, Bowman's space, glomerular basement membrane, mesangium, and arterioles were segmented, reconstructed, and quantitatively analyzed. Four types of glomerular cells, parietal epithelial cells, glomerular endothelial cells, podocytes, and mesangial cells were manually identified based on the size, shape, and position of the cell nuclei within the glomerular space. Several quantitativeparameters relating to cell nuclei were explored with the goal of finding potential classifiers to fully automate cell identification for future 3D reconstructions. We hypothesize that establishing and refining the GNSA will aid in revealing the global linkages among glomerular structures and supply a more robust understanding of the glomerulus as a unity that could doubtless deliver novel facets of glomerular diseases that have not been explored.