The Dlx homeobox genes have central roles in controlling patterning and differentiation of the brain and craniofacial primordia. In the brain, loss of Dlx function results in defects in the production, migration and differentiation of GABAergic neurons, that can lead to epilepsy. In the branchial arches, loss of Dlx function leads to craniofacial malformations that include trigeminal axon pathfinding defects. To determine how these genes function, we wish to identify the transcriptional circuitry that lies downstream of these transcription factors by comparing gene expression in wild type with Dlx mutant CNS and craniofacial tissues.
Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs.
No sample metadata fields
View SamplesAtopic dermatitis (AD) is a common pruritic dermatitis with macroscopically nonlesional skin that is often abnormal. Therefore, we used high-density oligonucleotide arrays to identify cutaneous gene transcription changes associated with early AD inflammation as potential disease control targets. Skin biopsy specimens analyzed included normal skin from five healthy nonatopic adults and both minimally lesional skin and nearby or contralateral nonlesional skin from six adult AD patients.
Early cutaneous gene transcription changes in adult atopic dermatitis and potential clinical implications.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.
Specimen part
View SamplesIt is widely believed that the molecular and cellular features of a tumor reflect its cell-of-origin and can thus provide clues about treatment targets. The retinoblastoma cell-of-origin has been debated for over a century. Here we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell typespecific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Importantly, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro. Our finding that retinoblastoma tumor cells express multiple neuronal differentiation programs that are normally incompatible in development suggests that the pathways that control retinal development and establish distinct cell types are perturbed during tumorigenesis. Therefore, the cell-of-origin for retinoblastoma cannot be inferred from the features of the tumor cells themselves. However, we now have a detailed understanding of the neuronal pathways that are deregulated in retinoblastoma and targeting the catecholamine and indolamine receptors or downstream components could provide useful therapeutic approaches in future studies. This example highlights the importance of comprehensive molecular, cellular and physiological characterization of human cancers with single cell resolution as we incorporate molecular targeted therapy into treatment regimens.
Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.
No sample metadata fields
View SamplesIt is widely believed that the molecular and cellular features of a tumor reflect its cell-of-origin and can thus provide clues about treatment targets. The retinoblastoma cell-of-origin has been debated for over a century. Here we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell typespecific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Importantly, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro. Our finding that retinoblastoma tumor cells express multiple neuronal differentiation programs that are normally incompatible in development suggests that the pathways that control retinal development and establish distinct cell types are perturbed during tumorigenesis. Therefore, the cell-of-origin for retinoblastoma cannot be inferred from the features of the tumor cells themselves. However, we now have a detailed understanding of the neuronal pathways that are deregulated in retinoblastoma and targeting the catecholamine and indolamine receptors or downstream components could provide useful therapeutic approaches in future studies. This example highlights the importance of comprehensive molecular, cellular and physiological characterization of human cancers with single cell resolution as we incorporate molecular targeted therapy into treatment regimens.
Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.
Specimen part
View SamplesIt is widely believed that the molecular and cellular features of a tumor reflect its cell-of-origin and can thus provide clues about treatment targets. The retinoblastoma cell-of-origin has been debated for over a century. Here we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell typespecific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Importantly, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro. Our finding that retinoblastoma tumor cells express multiple neuronal differentiation programs that are normally incompatible in development suggests that the pathways that control retinal development and establish distinct cell types are perturbed during tumorigenesis. Therefore, the cell-of-origin for retinoblastoma cannot be inferred from the features of the tumor cells themselves. However, we now have a detailed understanding of the neuronal pathways that are deregulated in retinoblastoma and targeting the catecholamine and indolamine receptors or downstream components could provide useful therapeutic approaches in future studies. This example highlights the importance of comprehensive molecular, cellular and physiological characterization of human cancers with single cell resolution as we incorporate molecular targeted therapy into treatment regimens.
Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.
Specimen part
View SamplesOur slr-2 dataset showed strong overrepresentation of genes previously identified in a serial analysis of gene expression (SAGE) intestinal library (McGhee et al., 2006) (p << 0.01); 812 genes were common to both data sets. Consistent with the deregulation of intestinal genes, we observed repression of several important metabolic pathways, including the TOR and insulin signaling networks, suggesting that slr-2(ku297) mutants experience metabolic stress. We also compared differentially regulated genes in slr-2 and lin-35 single mutants. Again, we saw a statistically significant overlap (p-value < 0.01); 261 genes were present in both data sets. Strikingly, > 75% of genes common both datasets showed expression changes in the same direction, although the common dataset contained an approximately equal mixture of up and downregulated genes. Furthermore, more than fifty genes common to the lin-35 and slr-2 datasets are known to have intestinal-associated functions. That some of these common intestinal genes were absent from the gut SAGE library could be due to differences in the developmental stage of the animals assayed (adults versus L1s) as well as experimental approaches (SAGE versus microarrays)
Coordinated regulation of intestinal functions in C. elegans by LIN-35/Rb and SLR-2.
No sample metadata fields
View SamplesPeripheral whole blood transcriptome profiles of pregnant women with normal pregnancy and spontaneous preterm birth from 10-18 weeks of gestational age enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
Transcriptome analysis of early pregnancy vitamin D status and spontaneous preterm birth.
Sex, Race
View SamplesPurpose: Communication between growth cones and their environment plays a central role in assembling neural circuits. We use Tandemly-Tagged Ribosome Affinity Purification (T-TRAP) of mRNA from R cells followed by RNA-seq for multiple time points during development to follow gene expression during target selection and synapse formation. Methods: We chose a ribosome trap method by modifying the N-terminus of the Drosophila ribosomal protein RpL10 with two tandemly arranged epitopes, 3X FLAG and GFP, separated by the Tobacco Etch Virus (TEV) protease site and expressed this in specific cell types using the GAL4/UAS system. cDNA libraries were prepared from mRNA associated with the affinity purified ribosomes and sequenced using an Illumina HiSeq 2000. We mapped raw reads to the D. melanogaster reference genome (release FB2013_01) with the gapped aligner Tophat. Only reads uniquely aligned were collected.Transcript expression levels were quantified using RPKM units using customized scripts written in Perl. Results: In this study, we observed massive changes in expression of cell surface proteins over short time scales (i.e. 5 fold differences in the expression of many hundreds of genes over 5 hr intervals) as R cell growth cones encounter the processes of many different neurons during their conversion from growth cones to synaptic terminals. In addition, to changes in transcripts encoding cell surface proteins, other mRNAs changed significantly as did non-coding RNAs (lincRNAs) associated with ribosomes. Although dramatic changes in transcript levels of presynaptic proteins were not observed preceding the onset of synapse formation, marked changes in the 3''-untranslated regions of these transcripts were seen. Conclusions: These studies provide a step towards merging traditional genetic and global genomic approaches to understanding cellular recognition underlying the assembly of neural circuits. Overall design: We chose 7 time points for RNA-seq analysis of R cells during pupal development corresponding to 24, 35, 40, 45, 53, 65 and 96 hrs after pupal formation (APF).
Rapid Changes in the Translatome during the Conversion of Growth Cones to Synaptic Terminals.
Age, Specimen part, Subject
View SamplesThese data show that the genes that distinguish myofibroblasts from fibroblasts are myriad, and that some genes not traditionally associated with myofibroblast differentiation may serve as novel therapeutic targets for fibrosing disorders.
Reversal of the Transcriptome by Prostaglandin E2 during Myofibroblast Dedifferentiation.
Specimen part, Cell line, Treatment
View Samples