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Updated: Jul 10, 2025
08:15
Estimation of Nephron Number in Whole Kidney using the Acid Maceration Method
Published on: May 22, 2019
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Acetyl-CoA is a key molecule for nephron progenitor cell pool maintenance
Fabiola Diniz1, Nguyen Yen Nhi Ngo1, Mariel Colon-Leyva1
1Section of Pediatric Nephrology, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
Nature Communications
|November 25, 2023
Summary
Acetyl-CoA metabolism is crucial for kidney development. Manipulating this pathway, particularly with sodium acetate, can maintain nephron progenitor cells and potentially prevent adult kidney disease.
Area of Science:
- Developmental Biology
- Metabolic Biochemistry
- Nephrology
Background:
- Nephron endowment at birth is critical for long-term renal and cardiovascular health.
- Nephron progenitor cell (NPC) fate is influenced by glycolysis, but the mechanism remains unclear.
Purpose of the Study:
- To elucidate the mechanism by which glycolysis modulation impacts NPC fate.
- To investigate the role of Acetyl-CoA metabolism in kidney development and nephrogenesis.
Main Methods:
- Combined RNA sequencing and quantitative proteomics to identify genes targeted by Wnt activation or glycolysis inhibition in NPCs.
- Utilized Six2Cre-mediated deletion of ATP-citrate lyase (Acly) and sodium acetate supplementation in mouse models.
Main Results:
- Identified 267 genes commonly affected by Wnt activation or glycolysis inhibition, converging at Acetyl-CoA.
- Glycolysis inhibition downregulated Mevalonate/cholesterol pathway genes and promoted NPC differentiation.
- Sodium acetate supplementation rescued glycolysis inhibition effects and countered Acly deletion impacts.
- Acly deletion led to NPC pool depletion, reduced glomeruli count, and increased Wnt4 expression.
Conclusions:
- Acetyl-CoA metabolism plays a pivotal role in kidney development.
- Targeting Acetyl-CoA metabolism offers potential strategies for manipulating nephrogenesis.
- Findings may lead to new approaches for preventing adult kidney disease.
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