D-3-Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is a necessary enzyme for de novo L-serine biosynthesis via the phosphorylated pathway. We demonstrated previously that Phgdh is expressed exclusively by neuroepithelium and radial glia in developing mouse brain and later mainly by astrocytes. Mutations in the human PHGDH gene cause serine deficiency disorders (SDD) associated with severe neurological symptoms such as congenital microcephaly, psychomotor retardation, and intractable seizures. We recently demonstrated that genetically engineered mice, in which the gene for Phgdh has been disrupted, have significantly decreased levels of serine and glycine, and exhibit malformation of brain such as microcephaly. The Phgdh null (KO) embryos exhibit lethal phenotype after gestational day 14, indicating that the phosphorylated pathway is essential for embryogenesis, especially for brain development. It is worth noting that the Phgdh knockout (KO) embryos primarily displayed microcephaly, which is the most conspicuous phenotype of patients with SDD. Thus, Phgdh KO mice are a useful animal model for studying the effect of diminished L-serine levels on development of the central nervous system and other organs. To better understand the mechanism underlying the molecular pathogenesis of SDD, we sought to examine whether gene expression is altered in the Phgdh KO mouse model. We identify genes that have altered expression in the head of the Phgdh KO embryos using the GeneChip array. Some of the genes identified by this method belong in functional categories that are relevant to the biochemical and morphological aberrations of the Phgdh deletion.
Inactivation of the 3-phosphoglycerate dehydrogenase gene in mice: changes in gene expression and associated regulatory networks resulting from serine deficiency.
Specimen part
View SamplesBACKGROUND:
Endometrial gene expression profiling in pregnant Meishan and Yorkshire pigs on day 12 of gestation.
Specimen part
View SamplesA first generation Affymetrix GeneChip Porcine genome array was used to profile the gene expression in porcine mesenteric lymph nodes over a time course of infection with S. Typhimurium, including the acute (8 hours post inoculation (hpi), 24 hpi, 48 hpi) and chronic (21 days post-inoculation (dpi)) stages of infection. Our objectives were to 1) identify and examine the stereotypical gene expression response within host MLN to S. Typhimurium infection, 2) characterize global host responses by revealing the specific features of the hosts innate immunity pathways, and 3) explore if and how S. Typhimurium may escape the host immune response and develop into a carrier state.
Global transcriptional response of porcine mesenteric lymph nodes to Salmonella enterica serovar Typhimurium.
Age
View SamplesTo understand the host transcriptional response to S. enterica serovar Choleraesuis (S. Choleraesuis), the first generation Affymetrix porcine GeneChip was used to identify differentially expressed genes in the mesenteric lymph nodes responding to infection at acute (8 hours (h), 24h, 48h post-inoculation (pi)) and chronic stages (21 days (d) pi)
Analysis of porcine transcriptional response to Salmonella enterica serovar Choleraesuis suggests novel targets of NFkappaB are activated in the mesenteric lymph node.
Age
View SamplesHESC-H9 and iPSC lines 3.5, 3.6 and 3.12 were analyzed using Affymetrix microarray before and after Definitive Endoderm (DE) formation. DE was induced using the ActivinA differentiation protocol described by D'Amour et al., 2006 (PMID: 16258519) Clustering analysis of transcripts that were differentially regulated during DE formation indicated that iPSC lines 3.5 and 3.12 differentiate in manner that is highly similar to HESC-H9 cells iPSC line 3.6 had a more divergent transcriptional profile.
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro.
No sample metadata fields
View SamplesAnalysis of the abh1 mutant Arabidopsis plants following treatment with 50 uM abscisic acid (ABA). ABH1 encodes the large (80kDa) subunit of the nuclear mRNA cap binding complex and affects early ABA signal transduction events (Hugouvieux et al., 2001, Cell 106, 477).
mRNA cap binding proteins: effects on abscisic acid signal transduction, mRNA processing, and microarray analyses.
No sample metadata fields
View SamplesA dataset for coordinated transcriptome analysis of the effect of ethanol on human embryonic cerebral slices in vitro and on the mouse embryonic cerebral cortex in a in vivo model.
Combined transcriptome analysis of fetal human and mouse cerebral cortex exposed to alcohol.
Time
View SamplesLarge-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1 knockout mice displayed phenotypes similar to those observed on ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes. Overall design: Total RNA-seq from dissected regions of the digestive tract, from wild-type and percc1-/- mice.
Noncoding deletions reveal a gene that is critical for intestinal function.
Specimen part, Subject
View SamplesGene expression from primary neuronal, astrocytic, oligodendrocytic and microglial cultures, as well as from RNA mixtures thereof.
Population-specific expression analysis (PSEA) reveals molecular changes in diseased brain.
Specimen part
View SamplesHigh environmental temperatures induce detrimental effects on various reproductive processes in cattle. According to the predicted global warming the number of days with unfavorable ambient temperatures will further increase. The objective of this study was to investigate effects of acute heat stress during the late pre-ovulatory phase on morphological, physiological and molecular parameters of dominant follicles in cycling cows during lactation. Eight German Holstein cows in established lactation were exposed to heat stress (28C) or thermoneutral conditions (15C) with pair-feeding for four days. After synchronization growth of dominant follicles was monitored by ultrasonogrphy, and 21 hrs after an induced pre-ovulatory LH surge antral steroid hormones and granulosa cell-specific gene expression profiles were determined. The data showed that the pre-ovulatory growth of dominant follicles and the estradiol, but not the progesterone concentrations tended to be slightly affected. mRNA microarray and hierarchical cluster analysis revealed distinct expression profiles in granulosa cells derived from heat stressed compared to pair-fed animals. Among the 255 affected genes heatstress-, stress- or apoptosis associated genes were not present. But instead, we found up-regulation of genes essentially involved in G-protein coupled signaling pathways, extracellular matrix composition, and several members of the solute carrier family as well as up-regulation of FST encoding follistatin. In summary, the data of the present study show that acute pre-ovulatory heat stress can specifically alter gene expression profiles in granulosa cells, however without inducing stress related genes and pathways and suggestively can impair follicular growth due to affecting the activin-inhibin-follistatin system.
Exposure of Lactating Dairy Cows to Acute Pre-Ovulatory Heat Stress Affects Granulosa Cell-Specific Gene Expression Profiles in Dominant Follicles.
Specimen part
View Samples