Organismal function is, to a great extent, determined by interactions among their fundamental building blocks, the cells. In?this work, we studied the cell-cell interactome of fetal placental trophoblast cells and maternal endometrial stromal cells, using single-cell transcriptomics. The placental interface mediates the interaction between two semiallogenic individuals, the mother and the fetus, and is thus the epitome of cell interactions. To study these, we inferred the cell-cell interactome? by assessing the gene expression of receptor-ligand pairs across cell types. Moreover, we find that the expression of G-protein coupled receptors is highly cell-type?specific, implying that ligand-receptor profiles could be a reliable tool for cell type identification. Furthermore, we find that uterine decidual cells represent a cell-cell interaction hub with a relatively large?number of potential incoming and outgoing signals. Decidual cells differentiate from their precursors, the endometrial stromal fibroblasts, during uterine preparation for pregnancy. We show that decidualization (even in vitro) enhances the ability ?to communicate with the fetus, as most of the receptors and ligands up-regulated during decidualization have their counterpart expressed in trophoblast cells. Among the signals transmitted, growth factors and immune signals dominate, suggesting a delicate balance of enhancing and suppressive signals. Finally, this study provides a rich resource of gene ?expression profiles of term intravillous and extravillous trophoblasts, including the transcriptome of the multinucleated syncytiotrophoblast. Overall design: We sequenced mRNA from primary human endometrial stromal fibroblasts and in vitro human decidualized stromal fibroblasts.
Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface.
Specimen part, Subject
View SamplesWe provide the tissue-level human placental transcriptomes from two term uncomplicated pregnancies. Tissue was collected at term C-section (no labor), from villous part of the placenta. Overall design: mRNA-seq of placenta from two term healthy pregnancies.
Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface.
Specimen part, Subject
View SamplesDiabetic embryopathy can affect any developing organ system, although cardiovascular malformations, neural tube defects and caudal dysgenesis syndrome are the most prominent congenital malformations. We hypothesize that the metabolic imbalance occurring in diabetic pregnancy de-regulates tissue specific gene expression programs in the developing embryo. In order to identify genes whose expression is affected by maternal diabetes, we analyzed gene expression profiles of diabetes-exposed mouse embryos by using Affymetrix microarrays. We identified 129 genes with altered expression levels; 21 genes had increased and 108 genes had decreased expression levels in diabetes-exposed embryos relative to controls. A substantial fraction of these genes (35) are essential for normal embryonic development as shown by functional studies in mouse models. The largest fraction of diabetes-affected genes was in transcription factor and DNA-binding/chromatin remodeling functional categories (19%), which directly affect transcription. These findings suggest that transcriptional regulation in the developing embryos is perturbed by maternal diabetes and that transcriptional regulation plays a major role in the responses of embryos to intrauterine exposure to diabetic conditions. Interestingly, we found the expression of hypoxia-inducible factor 1 (Hif1) deregulated in the embryos exposed to the conditions of maternal diabetes. Since hypoxic stress is associated with the complications of diabetic pregnancy, we performed a post-hoc analysis of our microarray data with a specific focus on known HIF1 target genes. Of 39 genes detected in our microarrays, the expression changes of 22 genes (20 were increased and two genes were decreased in diabetes-exposed embryos) were statistically significant. These results indicate that HIF1-regulated pathways are affected in diabetes-exposed embryos. These results strongly suggest that de-regulation of hypoxia/HIF1 activated pathways could be the one of the key molecular events associated with the exposure to the teratogenic intrauterine environment of a diabetic mother.
Maternal diabetes alters transcriptional programs in the developing embryo.
Specimen part
View SamplesExposure 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.
Maternal diabetes alters transcriptional programs in the developing embryo.
Specimen part, Disease, Disease stage
View SamplesThe growth in popularity of RNA expression microarrays has been accompanied by concerns about the reliability of the data especially when comparing between different platforms. Here we present an evaluation of the reproducibility of microarray results using two platforms, Affymetrix GeneChips and Illumina BeadArrays. The study design is based on a dilution series of two human tissues (blood and placenta), tested in duplicate on each platform. By a variety of measures the two platforms yielded data of similar quality and properties. The results of a comparison between the platforms indicate very high agreement, particularly for genes which are predicted to be differentially expressed between the two tissues. Agreement was strongly correlated with the level of expression of a gene. Concordance was also improved when probes on the two platforms could be identified as being likely to target the same set of transcripts of a given gene. These results shed light on the causes or failures of agreement across microarray platforms. The set of probes we found to be most highly reproducible can be used by others to help increase confidence in analyses of other data sets using these platforms.
Experimental comparison and cross-validation of the Affymetrix and Illumina gene expression analysis platforms.
No sample metadata fields
View SamplesThe present research is devoted to the identification of gene(s) severely affected by EMD mutations, leading to striated muscle laminopathies and more specifically the cardiomyopathy. For this purpose, we developped a large-scale gene expression approach on heart and skeletal tissues from Emd KO mouse model.
Activation of MAPK in hearts of EMD null mice: similarities between mouse models of X-linked and autosomal dominant Emery Dreifuss muscular dystrophy.
No sample metadata fields
View SamplesBackground: Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems. We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods: Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete Freunds adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results: Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions: These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression, demonstrating long-term effects of PAE on the CNS response under steady-state conditions and following an inflammatory insult. Key words: prenatal alcohol exposure (PAE), ethanol, inflammation, arthritis, gene expression, rat.
Prenatal alcohol exposure alters steady-state and activated gene expression in the adult rat brain.
Sex, Specimen part, Disease
View SamplesWe carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze.
Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy.
No sample metadata fields
View SamplesThis study takes on the problem of bridging transcriptional data to neuronal phenotype and function by using publicly available datasets characterizing distinct neuronal populations based on gene expression, electrophysiology and morphology. In addition, a non-published PatchSeq dataset of Pvalb-cre positive cells in CA1 was used, which is the dataset submitted here. Taken together, these datasets were used to identify cross-cell type correlations between these data modalities. Detected correlations were classified as “class-driven” if they could be explained by differences between excitatory and inhibitory cell classes, or “non-class driven” if they could be explained by gradient like phenotypic differences within cell classes. Some genes whose relationships to electrophysiological or morphological properties were found to to be specific to either excitatory or inhibitory cell types. The Patch Seq data specifically allowed simultaneous single-cell characterization of gene expression and electrophysiology, showing that the gene-property correlations observed across cell types were further predictive of within-cell type heterogeneity. Overall design: Patchseq data was collected from single cells of the mouse hippocampus CA1 in order to investigate correlations between gene expression patterns and electrophysiological properties of various interneuron cell classes 19 individual cells Re-analysis details included in supplementary file readme.txt.
Transcriptomic correlates of electrophysiological and morphological diversity within and across excitatory and inhibitory neuron classes.
Age, Specimen part, Subject
View Samples