Project description:The human colon contains an extensively diverse microbial ecosystem and one of the most numerous communities of immune cells. Studies have highlighted dynamic crosstalk between immune cells and commensals. While studies have demonstrated increasing diversity of microbiota from stomach to stool, whether and how immune cell heterogeneity and microbiota diversity change across the colon is undefined. Furthermore, whether these changes are co-depended in the healthy colon is unknown. Here, tissue samples are collected from caecum, transverse colon, sigmoid colon and mLN of cadaveric donors by the Cambridge Biorepository of Translational Medicine (CBTM). We use single cell RNA sequencing (10X genomics) to assess the dynamics of immune cell populations across the colon and in matching lymph nodes. Associated microbiome 16S sequencing data is available.
Project description:The human colon contains an extensively diverse microbial ecosystem and one of the most numerous communities of immune cells. Studies have highlighted dynamic crosstalk between immune cells and commensals. While studies have demonstrated increasing diversity of microbiota from stomach to stool, whether and how immune cell heterogeneity and microbiota diversity change across the colon is undefined. Furthermore, whether these changes are co-depended in the healthy colon is unknown. Here, tissue samples are collected from caecum, transverse colon, sigmoid colon and mLN of cadaveric donors by the Cambridge Biorepository of Translational Medicine (CBTM). We use single cell RNA sequencing (10X genomics) to assess the dynamics of immune cell populations across the colon and in matching lymph nodes. Associated microbiome 16S sequencing data is available.
Project description:The human colon contains an extensively diverse microbial ecosystem and one of the most numerous communities of immune cells. Studies have highlighted dynamic crosstalk between immune cells and commensals. While studies have demonstrated increasing diversity of microbiota from stomach to stool, whether and how immune cell heterogeneity and microbiota diversity change across the colon is undefined. Furthermore, whether these changes are co-depended in the healthy colon is unknown. Here, tissue samples are collected from caecum, transverse colon, sigmoid colon and mLN of cadaveric donors by the Cambridge Biorepository of Translational Medicine (CBTM). We use single cell RNA sequencing (10X genomics) to assess the dynamics of immune cell populations across the colon and in matching lymph nodes. Associated microbiome 16S sequencing data is available.
Project description:The human colon contains an extensively diverse microbial ecosystem and one of the most numerous communities of immune cells. Studies have highlighted dynamic crosstalk between immune cells and commensals. While studies have demonstrated increasing diversity of microbiota from stomach to stool, whether and how immune cell heterogeneity and microbiota diversity change across the colon is undefined. Furthermore, whether these changes are co-depended in the healthy colon is unknown. Here, tissue samples are collected from caecum, transverse colon, sigmoid colon and mLN of cadaveric donors by the Cambridge Biorepository of Translational Medicine (CBTM). We use single cell RNA sequencing (10X genomics) to assess the dynamics of immune cell populations across the colon and in matching lymph nodes. Associated microbiome 16S sequencing data is available.
Project description:The human colon contains an extensively diverse microbial ecosystem and one of the most numerous communities of immune cells. Studies have highlighted dynamic crosstalk between immune cells and commensals. While studies have demonstrated increasing diversity of microbiota from stomach to stool, whether and how immune cell heterogeneity and microbiota diversity change across the colon is undefined. Furthermore, whether these changes are co-depended in the healthy colon is unknown. Here, tissue samples are collected from caecum, transverse colon, sigmoid colon and mLN of cadaveric donors by the Cambridge Biorepository of Translational Medicine (CBTM). We use single cell RNA sequencing (10X genomics) to assess the dynamics of immune cell populations across the colon and in matching lymph nodes. Associated microbiome 16S sequencing data is available.
Project description:Gastric ulcer, which affect many of patients and is deeply related with gastric cancer, is caused by chronic gastric acid stimulation. Stomach fundus, the main body of stomach, is a major source of gastric acid and peptidase for food digestion. Recapturing the main body of stomach requires mainly 3 functionally differentiated cells; parietal (oxyntic) cells, chief (zymogenic) cells, and surface mucous foveolar (pit) cells. We have previously shown the induction of stomach tissue with functional secreting activities by directed differentiation of mouse embryonic stem cells (ES cells) to stomach primordium with both gut epithelium and splanchnic mesoderm. However, generating human stomach with fundus and such functions has been elucidated and a long-desired goal. Here, we describe the method for establishing human embryonic stem cell-derived stomach organoids with fundus gland structure. Along with mouse stomach development and de novo stomach generation from mouse ES cells in vitro, we observed gut-like structure formation from human embryonic stem cells by induction of both endoderm and mesoderm. These human embryonic gut could differentiate into stomach primordium by growth factor stimulation as well as stomach development, and form stomach tissue in three-dimensional organoid culture. Furthermore, these stomach organoids contain fundus-like gland with parietal cells and chief cells, some of secreting activities, and is transcriptionally close to human stomach. Human functional stomach derived from embryonic stem cells represent powerful tools for analying human stomach development, and gastric ulcer related disease including gastric tumorgenesis.
Project description:Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate aging associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 old (age>18 years) and 4 young (age 3-6 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in PBMC by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the old animals exhibited higher inflammatory biomarkers in plasma and lower CD4 T cells with altered distribution of naïve and memory T cell maturation subsets. The gut microbiome in old animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of old animals compared to the young. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile.