Project description:Ulcerative colitis is a chronic inflammatory disorder for which a definitive cure is still missing. This is characterized by an overwhelming inflammatory milieu in the colonic tract where a composite set of immune and non-immune cells orchestrate its pathogenesis. Over the last years, a growing body of evidence has been pinpointing gut virome dysbiosis as underlying its progression. Nonetheless, its role during the early phases of chronic inflammation is far from being fully defined. Here we show the gut virome-associated Hepatitis B virus protein X, most likely acquired after an event of zoonotic spillover, to be associated with the early stages of ulcerative colitis and to induce colonic inflammation in mice. It acts as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering mucosal immunity at the level of both innate and adaptive immunity. This study paves the way to the comprehension of the aetiopathogenesis of intestinal inflammation and encourages further investigations of the virome as a trigger also in other scenarios. Moreover, it provides a brand-new standpoint that looks at the virome as a target for tailored treatments, blocking the early phases of chronic inflammation and possibly leading to better disease management.
Project description:Necrotizing enterocolitis (NEC) is a severe intestinal disorder connected to a gut microbiota dysbiosis. Approximately 7-8% of very low birth weight (VLBW) infants are diagnosed with NEC with mortality rates reaching 20-50%. Fecal virome transfer (FVT) is an approach where the bacteria-free fecal fraction from a healthy donor is administered to a patient with a GM dysbiosis. FVT contains e.g. bacteriophages, eukaryotic viruses, and metabolites. Oral administered FVT from healthy milk-fed term pigs shows promising potential in preventing NEC in the preterm piglet model. However, efficacy and safety are inconsistent between experiments. In the current study, we aim to explore methods of creating reproducible FVT-like treatments and test if these act preventive against NEC and possess minimal side effects in the preterm piglet model. Using cesarean-delivered, formula-fed preterm pigs, we compare the NEC preventive effect of native donor fecal virome (nFV) with: 1) a defined bacteriophage cocktail targeting NEC-associated bacteria; and 2) a chemostat fecal virome propagation with lactose as the major carbohydrate source (cFV), and 3) chemostat fecal virome propagation with lactose and milk oligosaccharides (cFV-OS). All methods will be compared to control treatment with SM buffer (SM).
Project description:This study aims to explore the relationship between the respiratory virome, specifically bacteriophages, HERV and the host response in ARDS and to assess their value in predicting the prognosis of ARDS.
Project description:The wide application of pig disease model has caused a surge of interest in the study of derivation of pig induced pluripotent cells (iPSCs). Here we performed genome-wide analysis of gene expression profiling by RNA-seq and small RNA-seq and DNA methylation profile by MeDIP-seq in pig iPSCs through comparison with somatic cells. We identified mRNA and microRNA transcripts that were specifically expressed in pig iPSCs. We then pursued comprehensive bioinformatics analyses, including functional annotation of the generated data within the context of biological pathways, to uncover novel biological functions associated with maintenance of pluripotency in pig. This result supports that pig iPS have transcript profiles linked to ribosome, chromatin remodeling, and genes involved in cell cycle that may be critical to maintain their pluripotency, plasticity, and stem cell function. Our analysis demonstrates the key role of RNA splicing in regulating the pluripotency phenotype of pig cells. Specifically, the data indicate distinctive expression patterns for SALL4 spliced variants in different pig cell types and highlight the necessity of defining the type of SALL4 when addressing the expression of this gene in pig cells. MeDIP-seq data revealed that the distribution patterns of methylation signals in pig iPS and somatic cells along the genome. We identify 25 novel porcine miRNA, including pluripotency-related miR-302/367cluster up-regulated in pig iPSCs. At last, we profile the dynamic gene expression signature of pluripotent genes in the preimplantation development embryo of pig. The resulting comprehensive data allowed us to compare various different subsets of pig pluripotent cell. This information provided by our analysis will ultimately advance the efforts at generating stable naive pluripotency in pig cells.
Project description:Crossbreeding has been an effective method to improve crossbred performance in pig industry. To have a global view of a classic three-way crossbreeding system of Duroc x (Landrace x Yorkshire) (DLY), we identified SNPs for each pig breed and crossbred individual originated from a DLY pig family to estimate the influence of purebreds on crossbred offspring using whole-genome sequencing. To confirm the accuracy of the SNPs identified by whole-genome sequencing, therefore, we performed the porcine 60K BeadChip genotyping array (Illumina) for each sequenced pig individual.
Project description:It is evident that epigenetic factors, especially DNA methylation, play essential roles in obesity development. To learn systematic association of DNA methylation to obesity, we used pig as a model, and sampled eight diverse adipose tissues and two distinct skeletal muscle tissues from three pig breeds with distinguished fat levels: the lean Landrace, the fatty Rongchang, and the feral Tibetan pig. We sequenced 180 methylated DNA immunoprecipitation (MeDIP) libraries, generated 1,381 Gbp sequence data, and provided a genome-wide DNA methylation map for pig adipose and muscle studies. The analysis showed global similarities and differences between breeds, genders and tissues, and identified the differentially methylated regions (DMRs) that are preferentially located in intermediate CpG promoters and CpG island shores. The DMRs in promoters are highly associated to obesity development. We also analyzed methylation and regulation of the known obesity-related genes and predicted novel candidate genes. The comprehensive map here provides a solid base for exploring epigenetic mechanisms of adipose deposition and muscle growth. We collected eight diverse adipose tissues and two phenotypically distinct skeletal muscle tissues from three well-defined pig models with distinct fat rates, and studied genome-wide DNA methylation differences among breeds, males and females, and tissues.