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Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits in adipocytes using LipocyteProfiler

ABSTRACT: We report LipocyteProfiler, which is an unbiased high-throughput profiling assay, that uses a combination of dyes that make it amenable to large-scale and high-capacity profiling of lipid accumulating cell types. As exemplified by its application in adipocytes, we demonstrate that our customised morphometric approach is capable of surveying diverse cellular mechanisms by generating depot-specific, trait/process-specific and allele-specific morphological and cellular profiles. The approach demonstrated here paves the way to large-scale and high-capacity arrayed and pooled forward and reverse phenotypic genetic profiling in lipid storing cell types

ORGANISM(S): Homo sapiens

PROVIDER: GSE184089 | GEO | 2023/04/03

REPOSITORIES: GEO

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Project description:Kavšček2015 - Genome-scale metabolic model of Yarrowia lipolytica (iMK735) This model is described in the article: Optimization of lipid production with a genome-scale model of Yarrowia lipolytica. Kavšček M, Bhutada G, Madl T, Natter K. BMC Syst Biol 2015; 9: 72 Abstract: Yarrowia lipolytica is a non-conventional yeast that is extensively investigated for its ability to excrete citrate or to accumulate large amounts of storage lipids, which is of great significance for single cell oil production. Both traits are thus of interest for basic research as well as for biotechnological applications but they typically occur simultaneously thus lowering the respective yields. Therefore, engineering of strains with high lipid content relies on novel concepts such as computational simulation to better understand the two competing processes and to eliminate citrate excretion.Using a genome-scale model (GSM) of baker's yeast as a scaffold, we reconstructed the metabolic network of Y. lipolytica and optimized it for use in flux balance analysis (FBA), with the aim to simulate growth and lipid production phases of this yeast. We validated our model and found the predictions of the growth behavior of Y. lipolytica in excellent agreement with experimental data. Based on these data, we successfully designed a fed-batch strategy to avoid citrate excretion during the lipid production phase. Further analysis of the network suggested that the oxygen demand of Y. lipolytica is reduced upon induction of lipid synthesis. According to this finding we hypothesized that a reduced aeration rate might induce lipid accumulation. This prediction was indeed confirmed experimentally. In a fermentation combining these two strategies lipid content of the biomass was increased by 80%, and lipid yield was improved more than four-fold, compared to standard conditions.Genome scale network reconstructions provide a powerful tool to predict the effects of genetic modifications and the metabolic response to environmental conditions. The high accuracy and the predictive value of a newly reconstructed GSM of Y. lipolytica to optimize growth conditions for lipid accumulation are demonstrated. Based on these findings, further strategies for engineering Y. lipolytica towards higher efficiency in single cell oil production are discussed. This model is hosted on BioModels Database and identified by: MODEL1510060001. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits in adipocytes using LipocyteProfiler

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