Omics analysis with modeling reveals global adaptation of Aspergillus niger to hypoxic condition
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PROVIDER: PRJNA431301 | ENA |
REPOSITORIES: ENA
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Project description:Oxygen limitation is regarded as a useful strategy to improve enzyme production by mycelial fungus like Aspergillus niger. However, the intracellular metabolic response of A. niger to oxygen limitation is still obscure. To address this, the metabolism of A. niger was studied using multi-omics integrated analysis based on the latest GEMs (genome-scale metabolic model), including metabolomics, fluxomics and transcriptomics. Upon sharp reduction of the oxygen supply, A. niger metabolism shifted to higher redox level status, as well as lower energy supply, characterized by the accumulation of intermediates from the TCA cycle, down-regulation of genes for fatty acid synthesis and a rapid decrease of the specific growth rate. The gene expression of the glyoxylate bypass was activated, consistent with the increasing flux, which was assumed to reduce the NADH formation from TCA cycle and benefit maintenance of the cellular redox balance under hypoxic conditions. In addition, the relative fluxes of the EMP pathway were increased, which possibly relieved the energy demand for cell metabolism.
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Project description:Dendritic cells (DCs) are professional antigen-presenting cells whose activity is intrinsically linked to the microenvironment. Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues that creates a special microenvironment conditioning cell physiology. We studied the effects of hypoxia on the differentiation of human monocytes into DCs. Immature DCs were differentiated in vitro from human monocytes under normoxic (iDCs) or hypoxic (Hi-DCs) conditions and the gene expression profile was determined. Hi-DCs expressed novel hypoxia-inducible genes and were characterized by up-regulation of pathways associated with cell movement/migration. Keywords: stress response, cell differentiation
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Project description:Aspergillus fumigatus is an opportunistic, airborne pathogen causing invasive aspergillosis in immunocompromised patients. During the infection process A. fumigatus is challenged by hypoxic microenvironments occurring in inflammatory, necrotic tissue. To gain further insights into the adaptation mechanism, A. fumigatus was cultivated in an oxygen-controlled chemostat under hypoxic and normoxic conditions. Transcriptome analysis revealed significant increases in transcripts associated with cell wall polysaccharide metabolism, amino acid and metal ion transport, nitrogen metabolism and glycolysis. A concomitant reduction in transcript levels was observed with cellular trafficking and G-protein coupled signaling. To learn more about the functional roles of hypoxia-induced transcripts we deleted A. fumigatus genes putatively involved in reactive nitrogen species detoxification (fhpA), NAD+ regeneration (frdA, osmA) nitrogen metabolism (niaD, niiA) and respiration (rcfB). We show that the NO-detoxifying flavohemoprotein fhpA is strongly induced by hypoxia independent of the nitrogen source, but is dispensable for hypoxic survival. By deleting the nitrate reductase gene niaD, the nitrite reductase gene niiA and the two fumarate reductases genes frdA and osmA, we found that alternative electron acceptors such as nitrate and fumarate do not have a significant impact on growth of A. fumigatus during hypoxia, but that functional mitochondrial respiratory chain complexes are essential under these conditions. Inhibition studies indicated that primarily complex III and IV play a crucial role in the hypoxic growth of A. fumigatus.
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Project description:Dendritic cells (DCs) are professional antigen-presenting cells whose activity is intrinsically linked to the microenvironment. Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues that creates a special microenvironment conditioning cell physiology. We studied the effects of hypoxia on the differentiation of human monocytes into DCs and maturation into mature DCs. Mature DCs were differentiated in vitro from human monocytes under normoxic or hypoxic conditions and the gene expression profile was determined. The expression profile of mature dendritic cells under normoxia vs hypoxia was studied. Three healthy donors were used as biologial replicates.
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Project description:Tibetan chicken has a suite of adaptive features to tolerate the high-altitude hypoxic environment as a unique native breed in Qinghai-Tibet Plateau of China. Increasing evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have roles in hypoxic adaptation of high-altitude animals, though their exact contributions remain unclear. This study aims to uncover the global landscape of mRNAs, lncRNAs and miRNAs using transcriptome sequencing so as to construct a regulatory network of competing endogenous RNAs (ceRNAs) provide a new sight for the hypoxic adaptation of Tibetan chicken embryos. In the study, 354 differentially expressed mRNAs (DEGs), 389 differentially expressed lncRNAs (DELs) and 73 differentially expressed miRNAs (DEMs) were identified between Tibetan (TC) and Chahua chicken (CH). The functional analysis showed that several important DEMs and their targets of DELs and DEMs are involved in angiogenesis (include blood vessel development and blood circulation) and energy metabolism (include glucose, carbohydrate and lipid metabolism). The ceRNA network was then constructed with the predicted pairs of DEGs-DEMs-DELs which further revealed regulatory roles of these differentially expressed RNAs in hypoxic adaptation of Tibetan chicken.
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Project description:In this study, miRNA-seq technique was used to identify differentially expressed miRNAs (DE miRNAs) in cardiac muscle of the Tibetan pig (TP) and Yorkshire pig (YP), which were both raised in highland environments. We obtained 108 M clean reads and 372 unique miRNAs that included 210 known pre-miRNAs and 162 novel pre-miRNAs. In addition, 20 DE miRNAs, including 10 upregulated and 10 downregulated miRNAs, were identified by comparing TP and YP. Based on the expression abundance and differentiation between the two populations, we predicted their targets, and KEGG pathway analyses suggested that DE miRNAs between the Tibetan pigs and Yorkshire pigs are involved in hypoxia-related pathways, such as the MAPK, mTOR, and VEGF signaling pathways, cancer-related signaling pathways, etc. Five DE miRNAs were randomly selected to validate the veracity of miRNA-seq using real-time PCR. The results showed that the expression corresponds to the trend in miRNA-seq, hence the deep-sequencing methods were feasible and efficient. This study expanded the number of hypoxic-adaptation-related miRNAs in pig and indicated that the expression patterns of hypoxia-related miRNAs are significantly altered in the Tibetan pig. DE miRNAs may play important roles in hypoxic adaptation after migration to hypoxic environments.
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