Project description:As a single strand DNA binding protein, RPA1 participates in various cellular processes including DNA replication and DNA repair. However, the role of RPA1 in T cells is largely unknown. We generated a mouse model in which RPA1 was specifically deleted in T cells. Through single cell RNA sequencing, we reveal the immune landscape in RPA1 conditional knockout mice.
Project description:As a single strand DNA binding protein, RPA1 participates in various cellular processes including DNA replication and DNA repair. However, the role of RPA1 in T cells is largely unknown. We generated a mouse model in which RPA1 was specifically deleted in T cells. Through single cell RNA sequencing, we reveal the immune landscape in RPA1 conditional knockout mice.
Project description:As a single strand DNA binding protein, RPA1 participates various cellular processes including DNA replication and DNA repair.However, the role of RPA1 in T cell is largely unknown. We generate a mice model in which RPA1 was specifically deleted in T cell. Through single cell RNA sequencing, we reveal the immune landscape in RPA1 conditional knockout mice.
Project description:Replication protein A1 (RPA1) is a single-stranded DNA binding protein that is known to participate in DNA replication, recombination and damage repair. However, little is known about RPA1’s role in controlling chromatin architecture and gene transcription. Further, physiological functions of RPA1 in mouse tissues still remain exclusive. Here we show that Rpa1 heterozygous mice developed age-depended fatty liver disease and are more susceptible to hepatic steatosis in response to high-fat diet. Liver specific deletion of Rpa1 impairs fatty acid oxidation, leading to hepatic steatosis and high incidence of hepatocellular carcinoma. Transcriptome analysis identified down-regulation of fatty acid oxidation related genes. Cleavage Under Targets and Tagmentation (CUT&Tag) and Assay for transposase-accessible chromatin using sequencing (ATAC-seq) revealed that RPA1 binds and regulates chromatin accessibility in regulatory regions of a group of genes involved in lipid metabolism in liver. Further, down-regulation of RPA1 was found in patients with fatty liver disease. Thus, our results not only established that RPA1 is critical controller of chromatin architecture and regulator of gene transcription, but also provided new insights into the epigenetic mechanism of fatty liver disease, which could inform future therapy.
Project description:The spleen is considered a non-essential organ. However, its importance is increasingly clear, given the serious disorders caused by its absence or dysfunction, e.g., greater susceptibility to infections, thromboembolism and cancer. Also, non-functionality of the spleen can lead to higher risk of infection and death in patients with serious diseases, such as HIV, myeloma, and leukemia. Surgical techniques to preserve the spleen and maintain splenic function have become increasingly common. However, the morbidity and mortality associated with its absence and dysfunction are still high. We used the decellularization technique to obtain a viable splenic scaffold for recellularization in vitro and propose the idea of bioengineered spleen transplantation to the host. In our study, we demonstrated that the scaffold created after decellularization presents good removal of residual DNA and SDS, which are essential to prevent immunogenic responses and transplantation failure. Also, the main components of the splenic matrix, such as collagens, glycoproteins, and proteoglycans, were preserved. We observed the maintenance of important structural components such as white pulp, marginal zone and red pulp, in addition to the network of vascular ducts. The scaffold we developed was subsequently recellularized with stromal cells from the spleen of neonatal rats, demonstrating adhesion, proliferation and viability of cells in contact with the scaffold. Therefore, the splenic scaffold is very promising for use in studies on spleen reconstruction and transplantation, with the aim of complete recovery of splenic function.
Project description:Duck reovirus (DRV), a member of the genus Orthoreovirus in the family Reoviridae, was first isolated from Muscovy ducks. The disease associated with DRV causes great economic losses to the duck industry. However, the responses of duck (Cairna moschata) to the classical/novel DRV (C/NDRV) infections are largely unknown. To reveal the relationship of pathogenesis and immune response, the proteomes of duck spleen cells under the control and C/NDRV infections were compared. In total, 5986 proteins were identified, of which 5389 proteins were quantified. The different expressed proteins (DEPs) under the C/NDRV infections showed displayed various biological functions and diverse subcellular localizations. The proteins related to the serine protease system were siginificantly changed, suggesting that the activated serine protease system may play an important role under the C/NDRV infections. Furthermore, the differences in the responses to the C/NRDV infections between the duck liver and spleen cells were compared. Only a small number of common DEPs were identified in both liver and spleen cells, suggesting diversified pattern involved in the responses to the C/NRDV infections. However, the changes in the proteins involved in the serine protease systems were similar in both liver and spleen cells. Our data may give a comprehensive resource for investigating the responses to C/NDRV infections in ducks.