Project description:RNA was extracted from the meninges of mice from either Specific pathogen free or Germ free facilities or from the offspring of mice reconstituted with different human microbiomes.
Project description:Obesity and type 2 diabetes (T2D) remain major global healthcare challenges and developing therapeutics necessitate using nonhuman primate models. Here, we present proteomic analyses of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls.
Project description:HuMiChip2 was applied to analyze perform both strain-level identification and the functional profiling of human gut microbiomes from alcoholic cirrhosis patients and healthy individuals with alcohol abuse.
Project description:Primordial germ cells (PGCs) are the earliest embryonic progenitors in the germline. Correct formation of PGCs is critical to reproductive health as an adult. Recent work has shown that primate PGCs can be differentiated from pluripotent stem cells; however, a bioassay that supports their identity as transplantable germ cells has not been reported. Here, we adopted a xenotransplantation assay by transplanting single-cell suspensions of human and nonhuman primate embryonic Macaca mulatta (rhesus macaque) testes containing PGCs into the seminiferous tubules of adult busulfan-treated nude mice. We discovered that both human and nonhuman primate embryonic testis are xenotransplantable, generating colonies while not generating tumors. Taken together, this work provides two critical references (molecular and functional) for defining transplantable primate PGCs. These results provide a blueprint for differentiating pluripotent stem cells to transplantable PGC-like cells in a species that is amenable to transplantation and fertility studies.
Project description:We transplanted gut microbiota via fecal transfer from TD and ASD children into germ-free wild-type mice, and reveal that colonization with ASD microbiomes induces hallmark changes in sociability, vocalization, and stereotypies. The brains of mice receiving gut microbiota from ASD individuals display alternative splicing patterns for genes dysregulated in the human ASD brain.
Project description:Investigating alterations the intestinal microbiome in a diet induced obesity (DIO) rat model after fecal transplant from rats, which underwent Roux-Y-Gastric-Bypass surgery (RYGB). The microbiomes of the RYGB-donor rats, the DIO rats, and DIO rats after receiving the fecal transplant from the RYGB rats. As controls lean rats as well as lean, RYGB and DIO rats after antibiotics treatment were used.
Project description:The liver is a major site for synthesis, storage and redistribution of carbohydrates, proteins and lipids. In addition, it is well-known that maternal obesity (MO) increases risk of offspring cardiovascular disease (CVD), diabetes and obesity. However, the mechanisms by which the MO intrauterine environment predisposes offspring to CVD and metabolic dysregulation are unknown. The goal of this study was to assess the impact of MO on primate fetal liver and identify underlying molecular mechanisms by which MO increases disease risk. The goal of this study was to identify candidate molecular mechanisms underlying MO in the near-term non-human primate (NHP) fetal liver. This is the first study of NHP fetal MO livers using unbiased transcriptome analysis to quantify hepatic gene expression, identify dysregulated signaling pathways and potential miRNAs regulating the disrupted metabolic processes. Unbiased gene (arrays) and microRNA (miRNA; small RNA-Seq) abundances were quantified in near-term (0.9 Gestation (0.9G)) baboon fetal livers (control (CON) = 6; MO = 5) and subjected to pathway and network analyses (GeneSifter, Ingenuity® Pathway Analysis (IPA)) to identify a coordinated molecular response to MO. Lipid and glycogen content (CON = 16; MO = 16) were quantified by Computer Assisted Stereology Toolbox (CAST) in 0.9G livers. Pairwise comparisons showed 933 differentially expressed genes between CON and MO livers: 350 genes were upregulated and 583 were downregulated. Pathway analysis revealed upregulation of Wnt/β-catenin signaling and downregulation of tricarboxylic acid (TCA) cycle, proteasome, oxidative phosphorylation and glycolysis pathways in MO fetal livers compared with CON. Inversely expressed miRNAs that target genes in these pathways provide additional support for the importance of these pathways in fetal liver metabolic regulation. Consistent with the observed pathway changes in MO, we found hepatic lipid content was threefold greater in MO than CON fetal livers (p=0.02). Molecular genetic analyses of CON and MO fetal baboon livers revealed dysregulation of Wnt/β-catenin signaling, TCA cycle, proteasome, oxidative phosphorylation and glycolysis pathways in MO livers, all of which are central to fatty acid metabolism and lipid storage. The marked lipid accumulation in MO fetal livers supports our hypothesis that dysregulation of these pathways detrimentally impacts lipid management. Furthermore, our findings demonstrate the detrimental impact of MO on fetal liver development and suggest impaired hepatic function prior to birth.
