Project description:Abstract from manuscript Glioblastoma develops an immunosuppressive microenvironment that fosters tumorigenesis and resistance to current therapeutic strategies. Here we use multiplexed tissue imaging and single-cell RNA-sequencing to characterize the composition, spatial organization, and clinical significance of extracellular purinergic signaling in glioblastoma. We show that glioblastoma exhibit strong expression of CD39 and CD73 ectoenzymes, correlating with increased adenosine levels. Microglia are the predominant source of CD39, while CD73 is principally expressed by tumor cells, particularly in tumors with amplification of EGFR and astrocyte-like differentiation. Spatially-resolved single-cell analyses demonstrate strong spatial correlation between tumor CD73 and microglial CD39, and that their spatial proximity is associated with poor clinical outcomes. Together, this data reveals that tumor CD73 expression correlates with tumor genotype, lineage differentiation, and functional states, and that core purine regulatory enzymes expressed by neoplastic and tumor-associated myeloid cells interact to promote a distinctive adenosine-rich signaling niche and immunosuppressive microenvironment potentially amenable to therapeutic targeting.
Project description:Single cell-based studies have revealed tremendous cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degree of plasticity during organogenesis. The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts. Experimental manipulation of various developmental signals in the mouse embryo underscored important cellular plasticity in this embryonic territory. This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder. Nevertheless, the precise lineage hierarchy and succession of events leading to the segregation of an endoderm progenitor compartment into hepatic, biliary, and pancreatic structures are not yet established. Here, we combine computational modelling approaches with genetic lineage tracing to assess the tissue dynamics accompanying the ontogeny of the hepato-pancreato-biliary organ system. We show that a multipotent progenitor domain persists at the border between liver and pancreas, even after pancreatic fate is specified, contributing to the formation of several organ derivatives, including the liver. Moreover, using single-cell RNA sequencing we define a specialized niche that possibly supports such extended cell fate plasticity.
Project description:Interventions: Sevoflurane group:Nil;Propofol group:NIl
Primary outcome(s): Heterogeneity of immune cell RNA spectrum in local tissue and peripheral blood of tumor
Study Design: Non randomized control
Project description:We used droplet based Single cell RNA sequencing (10x genomics) on sorted cell from tumor and juxta tumor tissue to explore myeloid cell diversity and metabolism in tumor microenvironement
Project description:In the present study, scRNA-seq(single-cell RNA sequencing) was compared with snRNA-seq(single-nucleus RNA sequencing) in tumor tissue obtained from patients with HCC, using the 10X Genomics Chromium platform.
Project description:Aberrant DNA methylation is common in cancer. To associate DNA methylation with gene function, we performed RNAseq upon tumor tissue and matched normal tissues of two ccRCC (clear cell renal cell carcinoma) patients. To quantify 5mC and 5hmC level in each CG site at genome-wide level, we performed BS-seq and TAB-seq upon tumor tissue and matched normal tissues of two ccRCC (clear cell renal cell carcinoma) patients, respectively. mRNA profiles of tumor and matched normal tissues from two ccRCC patients were generated by deep sequencing, using Hiseq 2000. Single-nucleotide-resolution, whole-genome, 5mC and 5hmC profiles of tumor and matched normal tissues from two ccRCC (clear cell renal cell carcinoma) patients were generated by deep sequencing, using Hiseq 2000.
Project description:We used single-cell RNA-sequencing from tumors and matched normal tissue of 24 treatment-naïve patients to generate a single cell landscape of gastric cancer tumor microenvironment.
Project description:To invesitigate the additional paracaspase-independent tumor-promoting effect exist for Malt1. We thus collected E0771-Vector control tumor tissue, E0771 wildtype Malt1 (Malt1-WT) overexpression tumor tissue and E0771 paracaspase-deficient Malt1 (Malt1-PD) overexpression tumor tissue, and sorted out immune cells for 10× Genomics single cell RNA-sequencing (scRNA-seq).
