To define the molecular abnormalities at the stem cell level in polycythemia vera (PV), we examined global gene expression in circulating CD34+ cells from 19 JAK2 V617F-positive PV patients and 6 normal individuals using Affymetrix oligonucleotide microarray technology. We observed that CD34+ cell gene expression not only differed between the PV patients and the normal controls but also between men and women PV patients. Based on these gender-specific differences in gene expression, we were able to identify 102 genes differentially regulated concordantly by both men and women, which likely represent a core set of genes whose dysregulation is involved in the pathogenesis of PV. Gene expression was verified by Q-PCR of patient CD34+ cell RNA. Using the 102 gene set and unsupervised hierarchical clustering, the 19 PV patients could be separated in two groups that differed significantly with respect to hemoglobin level, thrombosis frequency, splenomegaly, splenectomy or chemotherapy exposure, leukemic transformation and overall survival. These results were confirmed using top scoring pairs, which identified a different set of 29 genes that independently segregated the 19 patients into the same two clinical groups: those with an aggressive form of the disease (7 patients), and those with an indolent form (12 patients).
Two clinical phenotypes in polycythemia vera.
Sex, Disease
View SamplesThere is differential expression of genes between cases and controls using microarray analysis, and genes that are crucial for host defence responses are significantly up-regulated in cases during pneumococcal infection.
Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case-control study.
Specimen part, Disease, Disease stage
View SamplesThe hemibiotrophic fungal pathogen Colletotrichum graminicola is the causal agent of anthracnose disease on maize stalks and leaves. After the formation of appressoria the host cell wall is penetrated by the conversion of appressorial turgor pressure into forceful ejection of a penetration peg. Subsequently, C. graminicola establishes biotrophic hyphae in the penetrated epidermis cell at around 36 hours post inoculation (hpi) until a switch of hyphal morphology and lifestyle takes place during the colonization of neighboring host cells at around 72 hpi. During the ensuing necrotrophic growth, dark necrotic lesions are formed that are visible as anthracnose symptoms. We used microarrays to detail the global programme of gene expression during the infection process of Colletotrichum graminicola in its host plant to get insight into the defense response of this compatible interaction and into the metabolic reprogramming needed to supply the fungus with nutrients.
Common Motifs in the Response of Cereal Primary Metabolism to Fungal Pathogens are not Based on Similar Transcriptional Reprogramming.
Time
View SamplesWe aimed to discover a combination of reliable and functionally important biomarkers of severe bacterial infection (SBI) using transcriptomics, and to evaluate their clinical validity.
Novel biomarker combination improves the diagnosis of serious bacterial infections in Malawian children.
Sex, Specimen part, Disease
View SamplesWe studied the transcriptional profile in yeast cells in response to heterologous expression of mammalian activated AKT1
Heterologous mammalian Akt disrupts plasma membrane homeostasis by taking over TORC2 signaling in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesWe studied the transcriptional profile in response to acute PtdIns-4,5P2 depletion induced by heterologous expression of a plasma membrane-directed version of mammalian PI3K catalytic subunit (p110-CAAX).
The yeast cell wall integrity pathway signals from recycling endosomes upon elimination of phosphatidylinositol (4,5)-bisphosphate by mammalian phosphatidylinositol 3-kinase.
No sample metadata fields
View SamplesThe transcriptome of the three atino80 allelic mutants was compared to that of wild-type and 50B Arabidopsis plants (see Fritsch et al. 2004). Since the transcriptomes of 50B and wild-type plants were found to be identical, we compared expression in the mutant with 50B and with wild-type without distinction. Therefore, we had four replicates of the wild type condition (50B line, wild-type) and two replicates for each of the mutant alleles (atino80-1, atino80-2 and atino80-3), all ecotype Columbia. All lines were profiled in duplicate (grown independently at 2-week-intervals).
The INO80 protein controls homologous recombination in Arabidopsis thaliana.
Age, Specimen part
View SamplesStriatal medium spiny neurons (MSN) are critically involved in motor control, and their degeneration is a principal component of Huntingtons disease. We find that the transcription factor Ctip2 (also known as Bcl11b) is central to MSN differentiation and striatal development. Within the striatum, it is expressed by all MSN, while it is excluded from essentially all striatal interneurons. In the absence of Ctip2, MSN do not fully differentiate, as demonstrated by dramatically reduced expression of a large number of MSN markers, including DARPP-32, FOXP1, Chrm4, Reelin, MOR1, GluR1, and Plexin-D1. Furthermore, MSN fail to aggregate into patches, resulting in severely disrupted patch-matrix organization within the striatum. Finally, heterotopic cellular aggregates invade the Ctip2-/- striatum suggesting a failure by MSN to repel these cells in the absence of Ctip2. In order to investigate the molecular mechanisms that underlie Ctip2-dependent differentiation of MSN and that underlie the patch-matrix disorganization in the mutant striatum, we directly compared gene expression between wild type and mutant striatum at P0. Because CTIP2-expressing MSN constitute 90-95% of the neurons within the striatum, we reasoned that we should be able to detect changes in medium spiny neuron gene expression in Ctip2 null mutants. We microdissected out small regions of striatum at matched locations in wild type and Ctip2-/- mutant littermates at P0 and investigated gene expression with Affymetrix microarrays. We selected the 153 most significant genes and further analyzed them to identify a smaller set of genes of potentially high biological relevance. In order to verify the microarray data and define the distribution of the identified genes in the striatum, we performed in situ hybridization or immunohistochemistry for 12 selected genes: Plexin-D1, Ngef, Nectin-3, Kcnip2, Pcp4L1, Neto1, Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, and Neurotensin. We find that all these genes are either specifically downregulated (Plexin-D1, Ngef, Nectin-3 Kcnip2, Pcp4L1, Neto1), or upregulated (Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, Neurotensin), in the Ctip2-/- striatum, confirming and extending the microarray results. Together, these data indicate that Ctip2 is a critical regulator of MSN differentiation, striatal patch development, and the establishment of the cellular architecture of the striatum.
Ctip2 controls the differentiation of medium spiny neurons and the establishment of the cellular architecture of the striatum.
No sample metadata fields
View SamplesThe restoration of catalytic activity to mutant enzymes by small molecules is well-established for in vitro systems. Here we show that the protein tyrosine kinase Src R388A mutant can be rescued in live cells using the small molecule imidazole. Cellular rescue of a v-Src homolog was rapid and reversible and conferred predicted oncogenic properties. Using chemical rescue in combination with mass spectrometry, six known Src kinase substrates were confirmed, and several new protein targets identified. Chemical rescue data suggests that c-Src is active under basal conditions. Rescue of R388A c-Src also allowed contributions of Src to the MAP kinase pathway to be clarified. This chemical rescue approach is likely to be of broad utility in cell signaling.
Chemical rescue of a mutant enzyme in living cells.
No sample metadata fields
View SamplesMutations of the transcriptional regulator Mecp2 cause the X-linked autism spectrum disorder Rett syndrome (RTT), and Mecp2 has been implicated in several other neurodevelopmental disorders. To identify potential target genes regulated directly or indirectly by MeCP2, we performed comparative gene expression analysis via oligonucleotide microarrays on Mecp2-/y (Mecp2-null) and wild-type CPN purified via fluorescence-activated cell sorting (FACS).
Reduction of aberrant NF-κB signalling ameliorates Rett syndrome phenotypes in Mecp2-null mice.
Specimen part
View Samples