Abstract: SA-PO0026
Glycolysis Controls Nephron Formation in Mouse Embryonic Kidneys and Human Kidney Organoids
Session Information
- Development, Stem Cells, and Regenerative Medicine
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 700 Development, Stem Cells, and Regenerative Medicine
Authors
- Tsuchida-Straeten, Nobuko, Universitat Heidelberg Medizinische Fakultat Heidelberg, Heidelberg, BW, Germany
- Hammer, Simon Hermann, Universitat Heidelberg Medizinische Fakultat Heidelberg, Heidelberg, BW, Germany
- Weber, Alexandra, Universitat Heidelberg Medizinische Fakultat Heidelberg, Heidelberg, BW, Germany
- Simons, Matias, Universitat Heidelberg Medizinische Fakultat Heidelberg, Heidelberg, BW, Germany
Background
The number of nephrons influences long-term renal health. It depends on the size of the nephron progenitor cell (NPC) pool and the efficiency of its differentiation into nephron epithelia. Although glycolytic regulation plays a critical role in determining NPC fate, the mechanisms underlying this process remain unclear.
Methods
Conditional 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (Pfkfb3) overexpression was used to assess the effect of increased glycolysis on mouse embryonic kidney development. Lactate measurements were performed for functional validation. Furthermore, in a modified ex vivo organ culture protocol for embryonic mouse kidney development as well as with an iPSC-based kidney organoid protocol, the effect of glycolysis inhibition on nephron formation was studied with the help of immunohistochemistry and qPCR.
Results
To test the morphogenetic role of glycolysis, we used conditional Pfkfb3 overexpression in the mouse embryo as well as pharmacological inhibition of Pfkfb3 with YN1 in an ex vivo kidney organ culture. While Pfkfb3 overexpression led to reduced ureteric bud (UB) branching, fewer nephrons and decreased organ size, YN1 treatment yielded the opposite effects. Morphometric analysis showed an increase and a depletion of the Six2-positive NPC compartment with glycolysis activation and suppression, respectively. In a human iPSC-derived kidney organoid model, YN1 treatment between day 7 and 12 similarly caused a higher number of Lhx1-positive nephrons. Additional, qPCR showed higher expression of WT1 and Lhx1 in YN1-treated organoids. Analysis at later stages confirmed a normal development of YN1-treated organoids. Glucose titration (0.05-10mM) assay using glucose-free iPSC culture media showed that nephron tubule formation during human renal organoid development requires an optimal range.
Conclusion
Our results suggest that high glycolysis rates in NPCs suppress differentiation into nephrons in mouse embryonic kidney and human renal organoids. This finding could not only be relevant for organoid protocol refinement but also for diabetic pregnancies. As in other developmental contexts glycolysis has been linked with Wnt signaling, we are currently studying the effects of glycolysis manipulation on Wnt signaling that has a key role in nephron formation.
Funding
- Government Support – Non-U.S.