Identification and characterization of Sall1-expressing cells present in the adult mouse kidney

Sall1 is a transcription factor that best identifies stem cells present in the mouse embryonic kidney. Mutations in Sall1 gene in mice can lead to dysgenesis of kidney, while in humans it results in the Townes-Brocks syndrome, which is associated with the kidney agenesis. Unlike the embryonic kidney, Sall1 expression in the adult kidney is largely unknown. We hypothesized that similar to the embryonic kidney, Sall1 expression can identify stem cells present in the adult kidney. Accordingly in this study, we identified Sall1-expressing cells in the adult mouse kidney, determined their role in kidney regeneration following ischemia-reperfusion injury (IRI), and sought the effect of age on Sall1 expression.

By immunofluorescence Sall1-expressing cells were identified in the proximal tubule at the cortico-medullary junction and constituted 0.5% of all tubular cells. Rare Sall1-positive cells were also identified in the outer cortex and distal tubules. Sall1 expression was not seen in the glomerular, interstitial, or vascular compartments. Following IRI, 90% of Sall1-expressing cells proliferated and 5% of Sall1-positive cells showed asymmetrical cell division with one of the two adjacent Sall1-positive cells incorporating chlorodeoxyuridine (CldU). Following IRI, there was an increase in Sall1 expression at 4 and 12 h, a decrease at 5 and 10 days, and baseline expression at day 30 by quantitative polymerase chain reaction (qRT-PCR) and Western blot analysis. There was no age-related change in Sall1 expression as determined by qRT-PCR, Western blot analysis, and immunofluorescence.

We conclude that Sall1-expressing cells are present in the adult mouse kidney, predominantly in the proximal tubules. Sall1-expressing cells proliferate following IRI and some of the Sall1-positive cells undergo asymmetrical cell division. Therefore, Sall1 is a promising marker for identification of stem cells present in the adult mouse kidney.