In this study we aimed to identify a baseline intrahepatic transcriptional signature associated with response in chronic hepatitis B patients treated with peginterferon-alfa-2a (peg-IFN) and adefovir.
An intrahepatic transcriptional signature of enhanced immune activity predicts response to peginterferon in chronic hepatitis B.
Specimen part, Disease, Disease stage
View SamplesLong non-coding RNAs (lncRNAs) are expressed in a highly tissue-specific manner where they function in various aspects of cell biology, often as key regulators of gene expression. In this study we established a role for lncRNAs in chondrocyte differentiation. Using RNA sequencing we identified a human articular chondrocyte repertoire of lncRNAs from normal hip cartilage donated by neck of femur fracture patients. Of particular interest are lncRNAs upstream of the master chondrocyte transcription factor SOX9 locus. SOX9 is an HMG-box transcription factor which is essential for chondrocyte development by directing the expression of chondrocyte specific genes. Two of these lncRNAs are upregulated during chondrogenic differentiation of MSCs. Depletion of one of these lncRNA, LOC102723505, which we termed ROCR (regulator of chondrogenesis RNA), by RNAi disrupted MSC chondrogenesis, concomitant with reduced cartilage-specific gene expression and incomplete matrix component production, indicating an important role in chondrocyte biology. Specifically, SOX9 induction was significantly ablated in the absence of ROCR, and overexpression of SOX9 rescued the differentiation of MSCs into chondrocytes. Our work sheds further light on chondrocyte specific SOX9 expression and highlights a novel method of chondrocyte gene regulation involving a lncRNA. Overall design: Human neck of femure fracture hip cartilage chondrocyte mRNA profile generated by RNA-seq
Expression analysis of the osteoarthritis genetic susceptibility mapping to the matrix Gla protein gene MGP.
Sex, Age, Specimen part, Subject
View SamplesPrevious studies identified a role for latent herpesvirus infection in cross-protection to infection and exacerbation of chronic inflammatory diseases. Here, we compared the gene expression signature from livers, spleens and brains of mice infected with wild-type gammaherpesvirus 68 (MHV68), a mutant virus defective in the establishment of latency (ORF73.stop) or mockulum. We identified over 600 genes differentially expressed in organs of mice latently infected with MHV68 and found distinct sets of genes linked to different pathways were altered in spleen compared to liver. Several of the most differentially expressed latency-specific genes (e.g. IFN, Cxcl9, Ccl5) are associated with known latency-specific phenotypes.
Latent gammaherpesvirus 68 infection induces distinct transcriptional changes in different organs.
Specimen part
View SamplesMicroRNA (miRNA) and endogenous siRNA (endo-siRNA) are two essential classes of small noncoding RNAs (sncRNAs) in eukaryotic organisms. The class of miRNA is diverse and there exist noncanonical miRNAs that bypass the canonical miRNA biogenesis pathway. In order to identify noncanonical miRNAs and endo-siRNAs responding to virus infection and study their potential function, we sequenced small-RNA species from cells lytically infected with murine gammaherpesvirus 68. In addition to 3 novel canonical miRNAs in mouse, two antisense miRNAs in virus and 25 novel noncanonical miRNAs, including miRNAs derived from tRNAs, snoRNAs and introns, in the host were identified. These noncanonical miRNAs exhibited features distinct from canonical miRNAs in the lengths and structures of miRNA hairpins as well as base pairings and first nucleotide preference. Many of the novel miRNAs are conserved in mammals. In addition to several known murine endo-siRNAs detected by the sequencing profiling, a novel locus in the mouse genome was identified to give rise to endo-siRNAs. This novel endo-siRNA locus is comprised of two tandem inverted B4 short interspersed nuclear elements (SINEs). Unexpectedly, the SINE-derived endo-siRNAs were found in a variety of sequencing data as well as virus-infected cells. Moreover, a murine miRNA was up-regulated more than 35 fold in infected than in mock-treated cells. The putative target genes of the viral and the up-regulated murine miRNAs were potentially involved in processes of gene transcription and protein phosphorylation and localized to membranes, suggesting their role in manipulating the host basal immune system during lytic infection. Our results extended the number of noncanonical miRNAs in mammals and shed new lights on their potential functions of lytic infection of MHV68. Overall design: Mouse NIH 3T12 cells infectd with MHV68 (3 samples) and mock-treated (2 samples) were examined. Noncanonical microRNAs and endogenous siRNAs discovery in lytic infection of murine gammaherpesvirus MHV68 (NC_001826.2).
Identification of novel microRNA-like molecules generated from herpesvirus and host tRNA transcripts.
Specimen part, Cell line, Subject
View SamplesThe Hessian fly (HF, Mayetiola destructor) is a biotrophic insect that interacts with wheat on a typical gene-for-gene basis. Identification of the genes which are differentially expressed during wheat-HF interactions may provide critical information to better understand the plant resistance mechanisms. Microarray analyses of transcripts, including those encoding various lipases, lipid transfer proteins, enzymes involved in oxylipin synthesis, and enzymes involved in wax and cutin synthesis, revealed that the abundance of many of these transcripts increased rapidly in resistant plants after HF attack, but did not change in susceptible plants.
Rapid mobilization of membrane lipids in wheat leaf sheaths during incompatible interactions with Hessian fly.
Specimen part, Treatment, Time
View SamplesTwo-dimensional (2D) nanomaterials, an ultrathin class of materials such as graphene, nanoclays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs), have emerged as a new generation of materials due to their unique properties relative to macroscale counterparts. However, little is known about the transcriptome dynamics following exposure to these nanomaterials. Here we investigate the interactions of 2D nanosilicates, a layered clay, with human mesenchymal stem cells (hMSCs) at the whole transcriptome level by high-throughput sequencing (RNA-seq). Analysis of cell-nanosilicate interactions by monitoring change in transcriptome profile uncovers key biophysical and biochemical cellular pathways triggered by nanosilicates. A widespread alteration of genes is observed due to nanosilicate exposure as more than 4,000 genes are differentially expressed. The change in mRNA expression levels reveal clathrin-mediated endocytosis of nanosilicates. Nanosilicate attachment to cell membrane and subsequent cellular internalization activate stress-responsive pathways such as mitogen activated protein kinase (MAPK), which subsequently directs hMSC differentiation towards osteogenic and chondrogenic lineages. This study provides transcriptomic insight on the role of surface-mediated cellular signaling triggered by nanomaterials and enables development of nanomaterials-based therapeutics for regenerative medicine. This approach in understanding nanomaterial-cell interactions, illustrates how change in transcriptomic profile can predict downstream effects following nanomaterial treatment. Overall design: Examination of affect of 2D nanosilicates on hMSCs
Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates.
Specimen part, Treatment, Subject
View SamplesWe tested the effects of co-infection on vaccine response to YFV-17D.
Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response.
Specimen part
View SamplesThe ductus arteriosus (DA) is a fetal vascular shunt that is located between the main pulmonary artery and the aorta. Oxygenated fetal blood from the placenta is shunted past the uninflated fetal lungs, crosses the DA, and is then available to the peripheral organs. In utero closure of the DA is deleterious, but postnatal closure of the DA is necessary for establishment of pulmonary circulation and the transition to newborn life.
Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone.
Specimen part
View SamplesFlower maturation consists of several events that contribute to reproductive success as flowers open, including petal expansion, stamen filament elongation, pollen release, nectary maturation, stigma growth, and gynoecium maturation to support pollen tube growth. The Arabidopsis transcription factors ARF6 (Auxin Response Factor 6) and ARF8 regulate all of these processes, in part by activating jasmonate biosynthesis. Jasmonates in turn activate genes encoding the transcription factors MYB21 and MYB24, which mediate a subset of the processes controlled by ARF6 and ARF8. This experiment was designed to characterize gene expression in flowers before and after they open, and to determine how arf6 arf8 and myb21 myb24 mutation combinations affect these gene expression patterns.
A regulatory network for coordinated flower maturation.
No sample metadata fields
View SamplesFluorescence-activated cell sorting of M4-GFP wing imaginal disc cells was used to recover a purified population of the cells that comprise the proneural clusters from which sensory organ precursors of the peripheral nervous system (PNS) arise. Whole-genome microarray analysis and in situ hybridization was then used to identify and verify a set of genes that are preferentially expressed in proneural cluster cells. Genes in this set encode proteins with a diverse array of implied functions, and loss-of-function analysis of two candidate genes shows that they are indeed required for normal PNS development.
Genetic programs activated by proneural proteins in the developing Drosophila PNS.
No sample metadata fields
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