Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesis.

Autor:	Votava JA; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA., John SV; Morgridge Institute for Research, Madison, WI, USA., Li Z; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA., Chen S; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA., Fan J; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA; Morgridge Institute for Research, Madison, WI, USA., Parks BW; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: brian.w.parks@wisc.edu.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2024 Mar; Vol. 65 (3), pp. 100525. Date of Electronic Publication: 2024 Feb 28.
DOI:	10.1016/j.jlr.2024.100525
Abstrakt:	The availability of genome-wide transcriptomic and proteomic datasets is ever-increasing and often not used beyond initial publication. Here, we applied module-based coexpression network analysis to a comprehensive catalog of 35 mouse genome-wide liver expression datasets (encompassing more than 3800 mice) with the goal of identifying and validating unknown genes involved in cholesterol metabolism. From these 35 datasets, we identified a conserved module of genes enriched with cholesterol biosynthetic genes. Using a systematic approach across the 35 datasets, we identified three genes (Rdh11, Echdc1, and Aldoc) with no known role in cholesterol metabolism. We then performed functional validation studies and show that each gene is capable of regulating cholesterol metabolism. For the glycolytic gene, Aldoc, we demonstrate that it contributes to de novo cholesterol biosynthesis and regulates cholesterol and triglyceride levels in mice. As Aldoc is located within a genome-wide significant genome-wide association studies locus for human plasma cholesterol levels, our studies establish Aldoc as a causal gene within this locus. Through our work, we develop a framework for leveraging mouse genome-wide liver datasets for identifying and validating genes involved in cholesterol metabolism. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu