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Integrated Transcriptome and Metabolome Analysis Reveals the Regulatory Mechanisms of FASN in Geese Granulosa Cells.

ABSTRACT: FASN plays a critical role in lipid metabolism, which is involved in regulating ovarian follicular development. However, the molecular mechanisms of how FASN regulate the function of ovarian follicular cells still remain elusive. In this study, by overexpression or interference of FASN in pre-hierarchical follicle granulosa cells (phGCs) and hierarchical follicle granulosa cells (hGCs), we analyzed their effects on the granulosa cell transcriptome and metabolome profiles using RNA-Seq and LC-MS/MS, respectively. The results showed that overexpression of FASN promoted proinflammatory factors expression by activating TLR3/IRF7 and TLR3/NF-κB pathways in phGCs, but only by activating TLR3/IRF7 pathways in hGCs. Then, necroptosis and apoptosis were triggered through the JAK/STAT1 pathway (induced by inflammatory factors) and BAK/caspase-7 pathway, respectively. The combined analysis of the metabolome and transcriptome revealed that FASN affected the demand of GCs for 5-hydroxytryptamine (5-HT) by activating the neuroactive ligand-receptor interaction pathway in two categorized GCs and only altering the metabolic pathway of tryptophan in phGCs, and ultimately participated in regulating the physiological function of geese GCs. Taken together, this study showed that the mechanisms of FASN regulating the physiological function of geese phGCs and hGCs were similar, but they also had some different characteristics.

SUBMITTER: Chen X

PROVIDER: S-EPMC9736573 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Integrated Transcriptome and Metabolome Analysis Reveals the Regulatory Mechanisms of FASN in Geese Granulosa Cells.

Chen Xi X Huang Kailiang K Hu Shenqiang S Lan Gang G Gan Xiang X Gao Shanyan S Deng Yan Y Hu Jiwei J Li Liang L Hu Bo B He Hua H Liu Hehe H Xia Lu L Wang Jiwen J

International journal of molecular sciences 20221125 23

FASN plays a critical role in lipid metabolism, which is involved in regulating ovarian follicular development. However, the molecular mechanisms of how FASN regulate the function of ovarian follicular cells still remain elusive. In this study, by overexpression or interference of FASN in pre-hierarchical follicle granulosa cells (phGCs) and hierarchical follicle granulosa cells (hGCs), we analyzed their effects on the granulosa cell transcriptome and metabolome profiles usi ...[more]

PMID: 36499045

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Project description:The walnut (Juglans regia) is an important oilseed tree species characterized by its extensive distribution, high oil yield, and nutrient-dense kernels, which provide substantial economic benefits. However, the rising incidence of late-spring frosts, exacerbated by global climate change, has adversely affected walnut yields. A comprehensive understanding of the regulatory mechanisms involved in bud dormancy, germination, and development is essential for developing strategies to mitigate the effects of late-spring frosts and for breeding frost-resistant cultivars. This study focused on W13, a protogynous walnut variety with early germination of dormant buds in spring, employing a combination of transcriptomic and hormone metabolomic analyses. Our results emphasized four key biological processes-cellular response to ethylene stimulus, phenylpropanoid metabolic process, ethylene-activated signaling pathway, and monooxygenase activity-along with several relevant pathways, including plant hormone signal transduction, flavone and flavonol biosynthesis, biosynthesis of secondary metabolites, and MAPK signaling pathway, all crucial for walnut bud germination. Additionally, bud germination is closely associated with alterations in various hormone signaling pathways, including abscisic acid, auxin, cytokinin, ethylene, gibberellins, jasmonic acid, and salicylic acid. By assessing hormone levels and gene expression at different developmental stages, we pinpointed potential regulatory genes and critical hormones associated with bud germination. Furthermore, through weighted correlation network analysis, we constructed a co-expression network, identifying gene modules specifically expressed during dormancy, germination, budding, and leafing phases. The hub genes within these modules are likely pivotal in regulating walnut bud germination. Our analysis also revealed that genes from various transcription factor families are central within the co-expression network, indicating their significant roles in the bud germination process. Correlation network analysis of hormone and gene further illuminated the mechanisms through which genes and hormones jointly influence walnut bud germination. These findings establish a crucial molecular basis for a more comprehensive understanding of the mechanisms governing germination and development in dormant walnut buds.

Project description:BackgroundRadix Ardisia (Jab Bik Lik Jib) is a common Miao medicine and is widely distributed in the Guizhou region of southern China. The botanical origin of Radix Ardisia includes the dry root and rhizome of Ardisia Crenata Sims (ACS) or Ardisia Crispa (Thunb.) A.DC. (AC), which are closely related species morphologically. However, the secondary metabolites in their roots are different from one another, especially the flavonoids, and these differences have not been thoroughly explored at the molecular level. This project preliminarily identified regulatory molecular mechanisms in the biosynthetic pathways of the flavonoids between ACS and AC using a multi-omics association analysis.MethodsIn this study, we determined the total levels of saponin, flavonoid, and phenolic in Radix Ardisia from different origins. Integrated transcriptome and metabolome analyses were used to identify the differentially expressed genes (DEGs) and differentially expressed metabolites (DEM). We also performed conjoint analyses on DEGs and DEMs to ascertain the degree pathways, and explore the regulation of flavonoid biosynthesis.ResultsThe total flavonoid and phenolic levels in ACS were significantly higher than in AC (P < 0.05). There were 17,685 DEGs between ACS vs. AC, 8,854 were upregulated and 8,831 were downregulated. Based on this, we continued to study the gene changes in the flavonoid biosynthesis pathway, and 100 DEGs involving flavonoid biosynthesis were differentially expressed in ACS and AC. We validated the accuracy of the RNA-seq data using qRT-PCR. Metabolomic analyses showed that 11 metabolites were involved in flavonoid biosynthesis including: Naringenin, Luteolin, Catechin, and Quercetin. A conjoint analysis of the genome-wide connection network revealed the differences in the types and levels of flavonoid compounds between ACS and AC. The correlation analysis showed that Naringenin, Luteolin, Catechin, and Quercetin were more likely to be key compounds in the flavonoid biosynthesis pathway also including 4CL, AOMT, CHS, CHI, DFR, F3'5'H, FLS, and LAR.ConclusionsThis study provides useful information for revealing the regulation of flavonoid biosynthesis and the regulatory relationship between metabolites and genes in the flavonoid biosynthesis pathway in Radix Ardisia from different origins.

Project description:BackgroundDorper and Tan sheep are renowned for their rapid growth and exceptional meat quality, respectively. Previous research has provided evidence of the impact of gut microbiota on breed characteristics. The precise correlation between the gastrointestinal tract and peripheral organs in each breed is still unclear. Investigating the metabolic network of the intestinal organ has the potential to improve animal growth performance and enhance economic benefits through the regulation of intestinal metabolites.ResultsIn this study, we identified the growth advantage of Dorper sheep and the high fat content of Tan sheep. A transcriptome study of the brain, liver, skeletal muscle, and intestinal tissues of both breeds revealed 3,750 differentially expressed genes (DEGs). The genes PPARGC1A, LPL, and PHGDH were found to be highly expressed in Doper, resulting in the up-regulation of pathways related to lipid oxidation, glycerophospholipid metabolism, and amino acid anabolism. Tan sheep highly express the BSEP, LDLR, and ACHE genes, which up-regulate the pathways involved in bile transport and cholesterol homeostasis. Hindgut content analysis identified 200 differentially accumulated metabolites (DAMs). Purines, pyrimidines, bile acids, and fatty acid substances were more abundant in Dorper sheep. Based on combined gene and metabolite analyses, we have identified glycine, serine, and threonine metabolism, tryptophan metabolism, bile secretion, cholesterol metabolism, and neuroactive ligand-receptor interaction as key factors contributing to the differences among the breeds.ConclusionsThis study indicates that different breeds of sheep exhibit unique breed characteristics through various physiological regulatory methods. Dorper sheep upregulate metabolic signals related to glycine, serine, and threonine, resulting in an increase in purine and pyrimidine substances. This, in turn, promotes the synthesis of amino acids and facilitates body development, resulting in a faster rate of weight gain. Tan sheep accelerate bile transport, reduce bile accumulation in the intestine, and upregulate cholesterol homeostasis signals in skeletal muscles. This promotes the accumulation of peripheral and intramuscular fat, resulting in improved meat quality. This work adopts a joint analysis method of multi-tissue transcriptome and gut metabolome, providing a successful case for analyzing the mechanisms underlying the formation of various traits.

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Dataset Information

Integrated Transcriptome and Metabolome Analysis Reveals the Regulatory Mechanisms of FASN in Geese Granulosa Cells.

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Integrated Transcriptome and Metabolome Analysis Reveals the Regulatory Mechanisms of <i>FASN</i> in <i>Geese</i> Granulosa Cells.

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