Abstract
The kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. Defects in kidney development are a significant cause of chronic kidney disease in children, which can lead to kidney failure that can only be treated by transplant or dialysis. A better understanding of molecular mechanisms that drive kidney development is important for designing strategies to enhance renal repair and regeneration. In this study, we profiled gene expression in the developing mouse kidney at embryonic day 14.5 at single-cell resolution. Consistent with previous studies, clusters with distinct transcriptional signatures clearly identify major compartments and cell types of the developing kidney. Cell cycle activity distinguishes between the “primed” and “self-renewing” sub-populations of nephron progenitors, with increased expression of the cell cycle-related genes Birc5, Cdca3, Smc2 and Smc4 in “primed” nephron progenitors. In addition, augmented expression of cell cycle related genes Birc5, Cks2, Ccnb1, Ccnd1 and Tuba1a/b was detected in immature distal tubules, suggesting cell cycle regulation may be required for early events of nephron patterning and tubular fusion between the distal nephron and collecting duct epithelia.
Highlights
The kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions
Cited[1] and Six[2] identify nephron progenitors, Lhx[1] and Pax[8] mark mixed/differentiating cells, Fxyd[2] and Hnf4a mark tubular cells, and podocytes are marked by Podxl and Nphs[1]
Consistent with this report, we found that nephron progenitor markers (Six[2], Cited[1], Crym) are expressed in cells in the stromal cluster, and that stromal markers are present in the nephron progenitor cluster (Meis[1], Foxd[1], Crabp1)
Summary
The kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. The mammalian kidney has evolved to provide critical adaptive regulatory mechanisms, such as the excretion of waste, and the maintenance of water, electrolyte and acid–base homeostasis to the body These functions require the coordinated development of specific cell types within a precise three-dimensional pattern. Nephrons form the functional units of the kidney and are derived from a nephron progenitor (NP) cell population, known as cap mesenchyme. These cells are capable of self-renewal, which is necessary to generate an appropriate number of nephrons during the course of embryogenesis and development. By the end of maturation, the glomerulus consists of four specified cell types: the fenestrated endothelium, mesangial cells, podocytes and parietal epithelial cells of the Bowman’s capsule[20–24]
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