Project description:To investigate the gene regulatory mechanisms driving T cell development, we generated single-cell transcriptomics and chromatin accessibility data from a human fetal thymus sample at 10 weeks of gestation.
Project description:Bufotoxin is an endogenous toxin made up of several physiologically active components that toads deploy as a defense against their natural enemies. Bufadienolides (BDS), which is isolated from bufotoxin, is an important anticancer drug, and other components such as bufotenine and alkaloids are also important drug resources. The distribution characteristics and biosynthesis of bufotoxins in the postauricular glands (PGs) of toads are not well understood. We examined the toad's PGs using the MADLI/MSI technique, a total of 1,872 components were found, and some pharmacological components were visible. These findings indicate that bufotoxins are primarily abundant in the plasma glands (pG) and epidermal tissues of the glands. By using single-cell sequencing, it was possible to create a single-cell atlas of 9316 PGs cells. These cells were then categorized into nine clusters using marker genes, and two types of epithelial cells were verified using in situ hybridization investigations. It was confirmed that cholesterol is a precursor component of BDS biosynthesis, we concentrated on the cholesterol metabolism component and postulated the primary bile acid pathway as a downstream biosynthesis pathway of BDS through transcriptomic studies of two pG and mucous glands (MG) with distinct secretory functions. Optimal and silenced genes for potential BDS synthesis pathways, toad toxin tryptamine and alkaloid biosynthesis, terpene skeleton and steroid hormones were identified by calculating the cellular coverage of genes. Our data demonstrate the metabolic mapping of bufotoxins in the PGs of the toad, and create the first single-cell atlas of PGs in the toad, providing a reference for the study of biosynthesis of natural active ingredients in animals.
Project description:This study investigates the role of dendritic cells (DCs) in anti-tumor immunity, focusing on the phosphatase SHP-1 and its regulation of signaling pathways and interactions with CD8+ T cells. Using conditional knockout mouse models and single-cell transcriptomics, we show that SHP-1 loss in conventional type 1 dendritic cells (cDC1s) and macrophages disrupts interferon responses, antigen presentation, and migratory programs, leading to impaired tumor rejection and reduced efficacy of PD-1 blockade. These findings provide mechanistic insights into dendritic cell biology within the tumor microenvironment (TME) and identify SHP-1 as a key regulator with implications for the design of DC-based cancer immunotherapies.