Project description:In Cystic Fibrosis (CF) patients, cycles of infection and inflammation lead to fatal lung damage. Here, we made use of a CF pig model to investigate proteome alterations in lung, lung-derived leukocytes and PBMCs.
Project description:Postweaning multisystemic wasting syndrome in pigs has devastated the swine industry since the 1990s. Porcine circovirus type 2 (PCV2) is the primary cause of this disease. MicroRNAs (miRNAs) are small noncoding RNAs that play important roles in regulating gene expression, especially at the post-transcription level. The expression profiles of miRNAs have been reported in porcine reproductive and respiratory syndrome, porcine parvovirus, and other pig diseases; however, the miRNA expression profiles in pigs infected with PCV2 have not been reported so far. The Laiwu pig (a Chinese indigenous pig breed) has different meat quality, adipogenesis, and disease-resistance from western commercial pig breeds. In this study, four small RNA libraries were constructed from the lung tissue of uninfected and infected Laiwu and Yorkshire/Landrace crossbred (YL) pigs. High-throughput sequencing and bioinformatics were used to determine the abundance and differential expression of miRNAs in the four libraries
Project description:Pulmonary vein stenosis (PVS) is a rare type of Pulmonary Hypertension (PH), which impacts the flow and pressure within the lung tissue and vasculature resulting in endothelial dysfunction and metabolic changes. We used a pig model in order to mimic PH post PVS using pulmonary vein banding (PVB) of the lower lobes for 12 weeks to investigate the alteration of pressure and flow which provides an impetus for development of PH. In order to develop site-specific therapies, our current study aimed to employ proteomics and metabolomics on both the upper and lower lobes of the pig lung to identify compartment-specific metabolic alterations.
Project description:To evaluate molecular consequences of insulin-deficient diabetes mellitus for lung tissue, we used clinically diabetic pig model of mutant INS gene induced diabetes of youth (MIDY). A multi-omics analysis combining in-depth data-independent acquisition proteomics, and targeted lipidomics revealed multiple dysregulated proteins and lipids and associated biological pathways in the MIDY lung.
Project description:Primary graft dysfunction (PGD), which is caused primarily by ischemia–reperfusion injury (IRI), is a major obstacle in lung transplantation. Here, we developed an orthotopic, single-lung transplant pig model to simulate prolonged cold IRI. After 24 hours of cold ischemia and 8 hours of warm reperfusion, the transplanted lung exhibited severe allograft injury. Subsequent single-cell RNA sequencing (scRNA-seq) revealed significant changes in alveolar macrophages after IRI, with prominently enriched ferroptosis pathways. Transmission electron microscopy (TEM) confirmed characteristic ferroptosis changes in lung macrophages, and decreased GPX4 expression in macrophages indicated increased susceptibility to ferroptosis. Overall, our pig orthotopic left lung transplant model effectively simulates IRI after transplantation, which offers a valuable platform for more detailed investigations of early reperfusion injury to pulmonary grafts. Moreover, we preliminarily demonstrated the importance of macrophage ferroptosis in IRI, suggesting that inhibiting macrophage ferroptosis may be a promising therapeutic strategy for lung IRI.
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:Investigation of the transcriptome profile of lung dendritic cells (DCs) of two genetically different pig breeds (Pietrain and Duroc) after PRRSV infection in vitro and determination of the temporal changes in transcriptional profiles.
Project description:The guinea pig (cavia porcellus) is an excellent experimental model for translation to many aspects of human physiology and disease yet there is limited experimental information regarding its proteome. In an effort to overcome this gap in our knowledge, we generated a comprehensive spectral library of the guinea pig proteome. Homogenates and tryptic peptide digests were prepared from 16 tissues (brain, colon, duodenum, adipose, kidney, large intestine, liver, lung, ovaries, pancreas, placenta, skeletal muscle, small intestine, stomach, heart, uterus) and subjected to >200 DDA runs. Analysis of >250,000 peptide-spectrum matches resulted in the construction of a library of 73594 peptides corresponding to 7667 proteins.