Podocyte-Parietal Epithelial Cell Interdependence in Glomerular Development and Disease

Podocytes and parietal epithelial cells (PECs) are among the few principal cell types within the kidney glomerulus, the former serving as a crucial constituent of the kidney filtration barrier and the latter representing a supporting epithelial layer that adorns the inner wall of Bowman's capsule. Podocytes and PECs share a circumscript developmental lineage that only begins to diverge during the S-shaped body stage of nephron formation-occurring immediately before the emergence of the fully mature nephron. These two cell types, therefore, share a highly conserved gene expression program, evidenced by recently discovered intermediate cell types occupying a distinct spatiotemporal gene expression zone between podocytes and PECs. In addition to their homeostatic functions, podocytes and PECs also have roles in kidney pathogenesis. Rapid podocyte loss in diseases, such as rapidly progressive GN and collapsing and cellular subtypes of FSGS, is closely allied with PEC proliferation and migration toward the capillary tuft, resulting in the formation of crescents and pseudocrescents. PECs are thought to contribute to disease progression and severity, and the interdependence between these two cell types during development and in various manifestations of kidney pathology is the primary focus of this review.