Sox9-Positive Progenitor Cells Play a Key Role in Renal Tubule Epithelial Regeneration in Mice

Cell Reports
Hyun Mi KangKatalin Susztak

Abstract

The kidney has a tremendous capacity to regenerate following injury, but factors that govern this response are still largely unknown. We isolated cells from mouse kidneys with high proliferative and multi-lineage differentiation capacity. These cells expressed a high level of Sox9. In regenerating kidneys, Sox9 expression was induced early, and 89% of proliferating cells were Sox9 positive. In vitro, Sox9-positive cells showed unlimited proliferation and multi-lineage differentiation capacity. Using an inducible Sox9 Cre line and lineage-tagging methods, we show that Sox9-positive cells can generate new daughter cells, contributing to the regeneration of proximal tubule, loop of Henle, and distal tubule segments but not to collecting duct and glomerular cells. Furthermore, inducible deletion of Sox9 resulted in reduced epithelial proliferation, more severe injury, and fibrosis development. In summary, we demonstrate that, in the kidney, Sox9-positive cells show progenitor-like properties in vitro and contribute to epithelial regeneration following injury in vivo.

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Citations

May 4, 2016·Nature Reviews. Nephrology·Maria EdelingKatalin Susztak
May 29, 2016·Kidney International·Melissa H Little, Pamela Kairath
Jul 28, 2016·European Journal of Pharmacology·Jennifer Eymael, Bart Smeets
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Nov 4, 2016·Journal of the American Society of Nephrology : JASN·Melissa Helen Little, Pamela Kairath
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Feb 16, 2020·Nature Reviews. Nephrology·Marta Ruiz-OrtegaRaul R Rodrigues-Diez
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Oct 9, 2019·International Journal of Molecular Sciences·Francesco GuzziElena Lazzeri
Oct 13, 2020·American Journal of Physiology. Renal Physiology·Ji Young KimNavjot Singh Pabla

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