During nephrogenesis, stem/progenitor cells differentiate and give rise to early nephron structures that segment to proximal and distal nephron cell types. Previously, we prospectively isolated progenitors from human fetal kidney (hFK) utilizing a combination of surface markers. However, upon culture nephron progenitors differentiated and could not be robustly maintained in vitro. Here, by cult...

Mammalian kidney organogenesis involves reciprocal epithelial-mesenchymal interactions that drive iterative cycles of nephron formation. Recent studies have demonstrated that the Six2 transcription factor acts cell autonomously to maintain nephron progenitor cells, whereas canonical Wnt signaling induces nephron differentiation. How Six2 maintains the nephron progenitor cells against Wnt-direct...

The neonatal mouse kidney retains nephron progenitor cells in a nephrogenic zone for 3 days after birth. We evaluated whether de novo nephrogenesis can be induced postnatally beyond 3 days. Given the long-term implications of nephron number for kidney health, it would be useful to enhance nephrogenesis in the neonate. We induced nephron reduction by cryoinjury with or without contralateral neph...

These studies, using in vivo micropuncture techniques in the Munich-Wistar rat, document the magnitude of changes in glomerular and tubular function and structure 24 h after approximately 75% nephron loss (Nx) and compared these results with those obtained in sham-operated rats. The contribution of either nephron hypertrophy or renal prostaglandin to these adjustments in nephron function was al...

Direct reprogramming involves the enforced re-expression of key transcription factors to redefine a cellular state. The nephron progenitor population of the embryonic kidney gives rise to all cells within the nephron other than the collecting duct through a mesenchyme-to-epithelial transition, but this population is exhausted around the time of birth. Here, we sought to identify the conditions ...

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are a polymorphic group of clinical disorders comprising the major cause of renal failure in children. Included within CAKUT is a wide spectrum of developmental malformations ranging from renal agenesis, renal hypoplasia and renal dysplasia (maldifferentiation of renal tissue), each characterized by varying deficits in nephron number....

BACKGROUND Endothelin, via endothelin A receptors (ETA), exerts multiple pathologic effects that contribute to disease pathogenesis throughout the body. ETA antagonists ameliorate many experimental diseases and have been extensively utilized in clinical trials. The utility of ETA blockers has been greatly limited, however, by fluid retention, sometimes leading to heart failure or death. To begi...

During nephrogenesis, multipotent mesenchymal nephron progenitors develop into distinct epithelial segments. Each nephron segment has distinct cell types and physiological function. In the current model of kidney development, Notch signaling promotes the formation of proximal tubules and represses the formation of distal tubules. Here, we present a novel role of Notch in nephrogenesis. We show ...

The nephron is the fundamental structural and functional unit of the kidney. Each mature nephron is patterned along a proximal-distal axis, with blood filteredat the proximal endand urine emerging from thedistal end. In order to filter theblood and produce urine, specialized structures are formed at specific proximal-distal locations along the nephron, including the glomerulus at the proximal e...

Factors which modify the excretion profiles of acute kidney injury biomarkers are difficult to measure. To facilitate biomarker choice and interpretation we modelled key modifying factors: extent of hyperfiltration or reduced glomerular filtration rate, structural damage, and reduced nephron number. The time-courses of pre-formed, induced (upregulated), and filtered biomarker concentrations wer...