Dataset Information

Genome-Wide Analysis of lncRNA and mRNA Expression During Differentiation of Abdominal Preadipocytes in the Chicken.

ABSTRACT: Long noncoding RNAs (lncRNAs) regulate adipogenesis and other processes associated with metabolic tissue development and function. However, little is known about the function and profile of lncRNAs during preadipocyte differentiation in the chicken (Gallus gallus). Herein, lncRNA and mRNA expression in preadipocytes at different stages of differentiation were analyzed using RNA sequencing. A total of 1,300,074,528 clean reads and 27,023 novel lncRNAs were obtained from 12 samples. The number of genes (1336 lncRNAs and 1759 mRNAs; 3095 in total) differentially expressed across various stages declined as differentiation progressed. Differentially expressed genes were found to be involved in several pathways related to preadipocyte differentiation that have been extensively studied, including glycerolipid metabolism, and the mammalian target of rapamycin, peroxisome proliferator-activated receptor, and mitogen-activated protein kinase signaling pathways. To our knowledge, some pathways are being reported for the first time, including the propanoate metabolism, fatty acid metabolism, and oxidative phosphorylation pathways. Furthermore, 3095 differentially expressed genes were clustered into eight clusters, and their expression patterns were determined through K-means clustering. Genes involved in the K2 cluster likely play important roles in preadipocyte differentiation. Six stage-specific modules related to A0 (day 0), A2 (day 2), and A6 (day 6) stages were identified, using weighted coexpression network analysis. Nine central, highly connected .genes in stage-specific modules were subsequently identified, including XLOC_068731, XLOC_022661, XLOC_045161, XLOC_070302, CHD6, LLGL1, NEURL1B, KLHL38, and ACTR6 This study provides a valuable resource for further study of chicken lncRNA and facilitates a better understanding of preadipocyte differentiation in the chicken.

SUBMITTER: Zhang T

PROVIDER: S-EPMC5345725 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Genome-Wide Analysis of lncRNA and mRNA Expression During Differentiation of Abdominal Preadipocytes in the Chicken.

Zhang Tao T Zhang Xiangqian X Han Kunpeng K Zhang Genxi G Wang Jinyu J Xie Kaizhou K Xue Qian Q

G3 (Bethesda, Md.) 20170310 3

Long noncoding RNAs (lncRNAs) regulate adipogenesis and other processes associated with metabolic tissue development and function. However, little is known about the function and profile of lncRNAs during preadipocyte differentiation in the chicken (<i>Gallus gallus</i>). Herein, lncRNA and mRNA expression in preadipocytes at different stages of differentiation were analyzed using RNA sequencing. A total of 1,300,074,528 clean reads and 27,023 novel lncRNAs were obtained from 12 samples. The num ...[more]

PMID: 28108554

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Project description:BackgroundAbdominal fat deposition depends on both the proliferation of preadipocytes and their maturation into adipocytes, which is a well-orchestrated multistep process involving many regulatory molecules. Circular RNAs (circRNAs) have emergingly been implicated in mammalian adipogenesis. However, circRNA-mediated regulation in chicken adipogenesis remains unclear. Our previous circRNA sequencing data identified a differentially expressed novel circRNA, 8:27,886,180|27,889,657, during the adipogenic differentiation of chicken abdominal preadipocytes. This study aimed to investigate the regulatory role of circDOCK7 in the proliferation and adipogenic differentiation of chicken abdominal preadipocytes, and explore its molecular mechanisms of competing endogenous RNA underlying chicken adipogenesis.ResultsOur results showed that 8:27,886,180|27,889,657 is an exonic circRNA derived from the head-to-tail splicing of exons 19-22 of the dedicator of cytokinesis 7 (DOCK7) gene, abbreviated as circDOCK7. CircDOCK7 is mainly distributed in the cytoplasm of chicken abdominal preadipocytes and is stable because of its RNase R resistance and longer half-life. CircDOCK7 is significantly upregulated in the abdominal fat tissues of fat chickens compared to lean chickens, and its expression gradually increases during the proliferation and adipogenic differentiation of chicken abdominal preadipocytes. Functionally, the gain- and loss-of-function experiments showed that circDOCK7 promoted proliferation, G0/G1- to S-phase progression, and glucose uptake capacity of chicken abdominal preadipocytes, in parallel with adipogenic differentiation characterized by remarkably increased intracellular lipid droplet accumulation and triglyceride and acetyl coenzyme A content in differentiated chicken abdominal preadipocytes. Mechanistically, a pull-down assay and a dual-luciferase reporter assay confirmed that circDOCK7 interacted with gga-miR-301b-3p, which was identified as an inhibitor of chicken abdominal adipogenesis. Moreover, the ACSL1 gene was demonstrated to be a direct target of gga-miR-301b-3p. Chicken ACSL1 protein is localized in the endoplasmic reticulum and mitochondria of chicken abdominal preadipocytes and acts as an adipogenesis accelerator. Rescue experiments showed that circDOCK7 could counteract the inhibitory effects of gga-miR-301b-3p on ACSL1 mRNA abundance as well as the proliferation and adipogenic differentiation of chicken abdominal preadipocytes.ConclusionsCircDOCK7 serves as a miRNA sponge that directly sequesters gga-miR-301b-3p away from the ACSL1 gene, thus augmenting adipogenesis in chickens. These findings may elucidate a new regulatory mechanism underlying abdominal fat deposition in chickens.

Project description:Local hypoxia has recently been reported to occur in the white adipose tissue (WAT) microenvironment during obesity. Adipocytes have a unique life cycle that reflects the different stages of adipogenesis in the WAT niche. Long non-coding RNAs (lncRNAs) play an important role in the cellular response to hypoxia. However, the differentially hypoxic responses of preadipocytes during adipogenesis and the potential role of lncRNAs in this process remain to be elucidated. Here, we evaluated the differentially hypoxic responses of primary hamster preadipocytes during adipogenesis and analyzed mRNA and lncRNA expression in same Ribo-Zero RNA-seq libraries. Hypoxia induced HIF-1? protein during adipogenesis and caused divergent changes of cell phenotypes. A total of 10,318 mRNAs were identified to be expressed in twenty libraries (five timepoints), and 3,198 differentially expressed mRNAs (DE mRNAs) were detected at five timepoints (hypoxia vs. normoxia). Functional enrichment analysis revealed the shared and specific hypoxia response pathways in the different stages of adipogenesis. Hypoxia differentially modulated the expression profile of adipose-associated genes, including adipokines, lipogenesis, lipolysis, hyperplasia, hypertrophy, inflammatory, and extracellular matrix. We also identified 4,296 lncRNAs that were expressed substantially and detected 1,431 DE lncRNAs at five timepoints. Two, 3, 5, 13, and 50 DE mRNAs at D0, D1, D3, D7, and D11, respectively, were highly correlated and locus-nearby DE lncRNAs and mainly involved in the cell cycle, vesicle-mediated transport, and mitochondrion organization. We identified 28 one-to-one lncRNA-mRNA pairs that might be closely related to adipocyte functions, such as ENSCGRT00015041780-Hilpda, TU2105-Cdsn, and TU17588-Ltbp3. These lncRNAs may represent the crucial regulation axis in the cellular response to hypoxia during adipogenesis. This study dissected the effects of hypoxia in the cell during adipogenesis, uncovered novel regulators potentially associated with WAT function, and may provide a new viewpoint for interpretation and treatment of obesity.

Dataset Information

Genome-Wide Analysis of lncRNA and mRNA Expression During Differentiation of Abdominal Preadipocytes in the Chicken.

Publications

Genome-Wide Analysis of lncRNA and mRNA Expression During Differentiation of Abdominal Preadipocytes in the Chicken.

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