Project description:Maternal diabetes during early pregnancy can cause birth defects, notably of the developing heart and nervous system. To recognize the gene expression differences that may be the basis for such birth defects, we performed RNA-Seq on mouse embryos of the Non-Obese Diabetic (NOD) strain. Mice of that strain spontaneously develop type I diabetes.
Project description:Here we asked whether the single early-life (pup day of life P5-P10) antibiotic pulse was sufficient to enhance Type-1 Diabetes (T1D) in Non Obese Diabetic (NOD) mice. Two sets of experimental samples were analyzed for changes in intestinal pathway expression using the NOD mouse model and Pulsed Antibiotic Therapy (PAT). NODPAT sought to describe the intestinal changes related to early life PAT treatment while the RESTORE experiment sought to restore an antibiotic-perturbed host and measure the intestinal expression changes over time. We provide evidence that maternal microbiota provides partial restoration of both the altered pup microbiota and its immunological phenotypes.
Project description:Children born to diabetic and obese or overweight mothers have a higher risk of heart disease at birth and later in life. Our previous work using chromatin immunoprecipitation sequencing revealed that late-gestation diabetes in combination with maternal high fat diet causes a distinct fuel-mediated epigenetic reprogramming of cardiac tissue during fetal cardiogenesis. We used gene expression profiling to investigate the overall transcriptional signature of newborn rat offspring exposed to the combination of maternal diabetes and maternal high fat diet.
Project description:Type 1 diabetes (T1D) is an autoimmune disease triggered by T cell reactivity to protein antigens produced by the β-cells. Here we present a chronological compendium of transcriptional profiles from islets of Langerhans isolated from non-obese diabetic (NOD) mice ranging from 2 wks up to diabetes and compared to controls. Parallel analysis was made of cellular components of the islets. Myeloid cells populated the islets early during development in all mouse strains. This was followed by a type I interferon signature detectable at 4-6 wks of age only in diabetes susceptible mice. Concurrently, CD4 T cells were found within islets, many in contact with intra-islet antigen presenting cells. Early cellular signs of islet reactivity were detected by six wks. By 8 wks, NOD islets contained all major leukocytes populations and an inflammatory gene signature. This work establishes the natural transcriptional signature of T1D and provides a resource for future research. 57 RNA samples isolated from the pancreatic islets of langerhans of experimental mice: 2-18 wk old non-obese diabetic (NOD) and newly diabetic NOD were compared to controls: NOD.RAG-/-, B6.g7 and C57BL/6. There were 3 or 6 biological replicates per condition. All mice were female. All data was normalized using RMA in Arraystar. Data table includes normalized probe intensity for every probe.
Project description:Type 1 and type 2 diabetes (T1D and T2D) share pathophysiological characteristics, yet mechanistic links have remained elusive. T1D results from autoimmune destruction of pancreatic beta cells, while beta cell failure in T2D is delayed and progressive. Here we find a new genetic component of diabetes susceptibility in T1D non-obese diabetic (NOD) mice, identifying immune-independent beta cell fragility. Genetic variation in Xrcc4 and Glis3 alter the response of NOD beta cells to unfolded protein stress, enhancing the apoptotic and senescent fates. The same transcriptional relationships were observed in human islets, demonstrating the role for beta cell fragility in genetic predisposition to diabetes.
Project description:Exposure to maternal diabetes during pregnancy alters transcriptional profiles in the developing embryo. The enrichment, within the set of de-regulated genes, of those encoding transcriptional regulatory molecules provides support for the hypothesis that maternal diabetes affects specific developmental programs. We compared E10.5 cntrol embryos to E10.5 embryos from diabetic pregnancies in the FVB mouse strain. Diabetes was induced in 7-9 week old female FVB mice by streptozotocin. Dams whose blood glucose levels exceeded 250 mg/dl were set up for mating. Embryos were dissected at E10.5 and total RNA was isolated. Equal amounts of RNA prepared from 3 individual embryos were pooled into one sample; each embryo was from a different pregnancy. Three pools were constructed for a total of nine embryos from diabetic pregnancies, and independently three pools for control embryos.
Project description:Lipidomics analysis of three models of insulitis and type 1 diabetes progression: isolated human islets and EndoC-betaH1 beta-cells treated with the proinflammatory cytokines IL-1beta and IFN-gamma, and islets from non-obese diabetic (NOD) mice isolated before the onset of diabetes. Samples were extracted with chloroform:methanol:water solution and analyzed by LC-MS/MS. Lipids were identified with LIQUID and quantification was performed with MZmine.
Project description:Maternal diabetes is associated with a wide range of fetal and neonatal adverse effects including pulmonary disturbances. To investigate the effects of maternal diabetes on neonatal lung gene expression profile, we performed microarray analysis on the lungs of 14-day-old rats born to diabetic dam. Keywords: disease state analysis Four neonatal lungs exposed to maternal diabetes and four control lungs were analyzed.
Project description:Exposure to maternal diabetes during pregnancy alters transcriptional profiles in the developing embryo. The enrichment, within the set of de-regulated genes, of those encoding transcriptional regulatory molecules provides support for the hypothesis that maternal diabetes affects specific developmental programs. We compared E10.5 cntrol embryos to E10.5 embryos from diabetic pregnancies in the FVB mouse strain.
Project description:Analysis of umbilical cord tissue in newborns of type 1 diabetic mothers at gene expression level. The hypothesis tested in the present study was that intrauterine diabetic milieu may effect of fetal umbilical cord gene expression, and via umbilical cord, the alterations may be produced in other fetal tissues as well. Results provide an information of the differentially expressed genes and enriched pathways, such as the dowregulated genes on the pathway on blood vessel development in umbilical cords from diabetic pregnancies. Umbilical cord tissue was collected after elective ceasarean section and was immediately flash frozen in liquid nitrogen and stored at -80C until total RNA extraction from the whole tissue sample. Six cords exposed to maternal diabetes (DM) and six control cords (C) from healthy pregnancies were analyzed.