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Characterization of biological pathways regulating acute cold resistance of zebrafish

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Danio rerio

PROVIDER: GSE168357 | GEO | 2021/03/06

REPOSITORIES: GEO

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Characterization of Biological Pathways Regulating Acute Cold Resistance of Zebrafish

Project description:Low temperature stress represents a major threat to the lives of both farmed and wild fish species. However, biological pathways determining the development of cold resistance in fish remain largely unknown. Zebrafish larvae at 96 hpf were exposed to lethal cold stress (10 °C) for different time periods to evaluate the adverse effects at organism, tissue and cell levels. Time series RNA sequencing (RNA-seq) experiments were performed to delineate the transcriptomic landscape of zebrafish larvae under cold stress and during the subsequent rewarming phase. The genes regulated by cold stress were characterized by progressively enhanced or decreased expression, whereas the genes associated with rewarming were characterized by rapid upregulation upon return to normal temperature (28 °C). Genes such as trib3, dusp5 and otud1 were identified as the representative molecular markers of cold-induced damages through network analysis. Biological pathways involved in cold stress responses were mined from the transcriptomic data and their functions in regulating cold resistance were validated using specific inhibitors. The autophagy, FoxO and MAPK (mitogen-activated protein kinase) signaling pathways were revealed to be survival pathways for enhancing cold resistance, while apoptosis and necroptosis were the death pathways responsible for cold-induced mortality. Functional mechanisms of the survival-enhancing factors Foxo1, ERK (extracellular signal-regulated kinase) and p38 MAPK were further characterized by inhibiting their activities upon cold stress and analyzing gene expression though RNA-seq. These factors were demonstrated to determine the cold resistance of zebrafish through regulating apoptosis and p53 signaling pathway. These findings have provided novel insights into the stress responses elicited by lethal cold and shed new light on the molecular mechanisms underlying cold resistance of fish.

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Characterization of biological pathways regulating acute cold resistance of zebrafish - experiment 2

Project description:This experiment was performed to investigate the functional mechanisms of the critical pathways including ERK, p38 MAPK and the transcription factor Foxo1 in enhancing cold resistance of zebrafish.Specific inhibitors of these pathways were used to treat zebrafish larvae under both normal and low temperatures to investigate the functions of these pathways in regulating cold stress response.

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Genome-wide studies reveal novel biological pathways regulated by SIN3 isoforms

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Project description:BACKGROUND: Temperature is one of key environmental parameters that affect the whole life of fishes and an increasing number of studies have been directed towards understanding the mechanisms of cold acclimation in fish. However, the adaptation of larvae to cold stress and the cold-specific transcriptional alterations in fish larvae remain largely unknown. In this study, we characterized the development of cold-tolerance in zebrafish larvae and investigated the transcriptional profiles under cold stress using RNA-seq. RESULTS: Pre-exposure of 96 hpf zebrafish larvae to cold stress (16°C) for 24 h significantly increased their survival rates under severe cold stress (12°C). RNA-seq generated 272 million raw reads from six sequencing libraries and about 92% of the processed reads were mapped to the reference genome of zebrafish. Differential expression analysis identified 1,431 up- and 399 down-regulated genes. Gene ontology enrichment analysis of cold-induced genes revealed that RNA splicing, ribosome biogenesis and protein catabolic process were the most highly overrepresented biological processes. Spliceosome, proteasome, eukaryotic ribosome biogenesis and RNA transport were the most highly enriched pathways for genes up-regulated by cold stress. Moreover, alternative splicing of 197 genes and promoter switching of 64 genes were found to be regulated by cold stress. A shorter isoform of stk16 that lacks 67 amino acids at the N-terminus was specifically generated by skipping the second exon in cold-treated larvae. Alternative promoter usage was detected for per3 gene under cold stress, which leading to a highly up-regulated transcript encoding a truncated protein lacking the C-terminal domains. CONCLUSIONS: These findings indicate that zebrafish larvae possess the ability to build cold-tolerance under mild low temperature and transcriptional and post-transcriptional regulations are extensively involved in this acclimation process.

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MicroRNAs and their isomiRs function cooperatively to target common biological pathways

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