The very limited ability of adult podocytes to proliferate in vivo is clinically significant because podocytes form a vascular barrier that is functionally critical to the nephron, podocyte hypoplasia is a characteristic of disease, and inadequate regeneration of podocytes is a major cause of persistent podocyte hypoplasia. Excessive podocyte loss or inadequate replacement leads to glomerulosclerosis in many progressive kidney diseases. Thus, restoration of podocyte cell density almost certainly is reliant on regeneration by podocyte progenitors. However, such putative progenitors have remained elusive until recently. In this review, we describe the developmental processes leading to podocyte and parietal epithelial cell (PEC) formation during glomerulogenesis. We compare evidence that in normal human kidneys PECs expressing progenitor markers CD133 and CD24 can differentiate into podocytes in vitro and in vivo, with evidence from animal models suggesting a more limited role of the PEC's capacity to serve as a podocyte progenitor in adults. We highlight tantalizing new evidence that specialized vascular wall cells of afferent arterioles, including those that produce renin in healthy kidney, provide a novel local progenitor source of new PECs and podocytes in response to podocyte hypoplasia in the adult, and draw comparisons with glomerulogenesis.
Keywords: Glomerulus; WT-1; cells of renin lineage; glomerulosclerosis; parietal epithelial cells; proteinuria.
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