The microarray analysis was designed to test the effects of HES5.3 siRNAs, Atoh7 siRNAs and nt siRNAs on gene expression in embryonic chick retina.
A positive feedback loop between ATOH7 and a Notch effector regulates cell-cycle progression and neurogenesis in the retina.
Age, Specimen part
View SamplesWe attempted to identify alterations in gene expression that occur during the progression from normal breast to ductal carcinoma in situ (DCIS) with the aim to elucidate significant genes and pathways underlying the premalignant transformation. To determine the expression changes that are common to multiple DCIS models (MCF10.DCIS, SUM102 and SUM225) and normal mammary epithelial cells (MCF10A), we grew the cells in three dimensional overlay culture with reconstituted basement membrane and used the extracted RNA for 76 cycles of deep sequencing (mRNA-Seq) using Illumina Genome Analyzer GAIIx. Analysis of mRNA-Seq results showed 295 consistently differentially expressed transcripts in DCIS models as compared to MCF10A. These differentially expressed genes are associated with a number of signaling pathways such as integrin, fibroblast growth factor and TGFß signaling. Many differentially expressed transcripts in DCIS were found to be involved in cell-cell signaling, cell-cell adhesion and cell proliferation. We further investigated ALDH5A1 gene that encodes for the enzyme, aldehyde dehydrogenase 5A1, which is involved in glutamate metabolism. Further, inhibition of ALDH5A1 with different pharmacological drugs resulted in significant inhibition of cell growth and proliferation in the DCIS models. Overall design: Four cell lines examined: normal mammary epithelial cell line (one sample) and three ductal carcinoma in situ cell lines (three samples). Each sample has two duplicates
RNA-Seq of human breast ductal carcinoma in situ models reveals aldehyde dehydrogenase isoform 5A1 as a novel potential target.
Disease, Cell line, Subject
View SamplesThe 6-hydroxydopamine (6OHDA) rat model of parkinsonism is among the first, and most commonly used, animal models of Parkinsons disease. It provides insight into the compensatory changes that occur in the brain after dopamine (DA) neuron degeneration. In order to better define the consequences of substantia nigra DA neuron loss on the neural and glial populations during and following nigrostriatal degeneration, tissue was collected and evaluated from the substantia nigra of 6OHDA or vehicle treated, or nave rats at 1, 2, 4, 6 & 16 weeks.
The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes.
Sex, Specimen part
View SamplesAluminum toxicity is one of the major limiting factors for many crops worldwide. The primary symptom of Al toxicity syndrome is the inhibition of root growth, leading to poor water and nutrient absorption. The causes of this inhibition are still elusive, with several biochemical pathways being affected and with a significant variation between species. Most of the work done so far to investigate the genes responsible for Al tolerance used hydroponic culture. Here we evaluated plant responses using soil as substrate, which is a condition closer to the field reality.
Transcriptional profile of maize roots under acid soil growth.
Specimen part
View SamplesWhile long noncoding RNAs (lncRNAs) and mRNAs share similar biogenesis pathways, these two transcript classes differ in many regards. LncRNAs are less conserved, less abundant, and more tissue specific than mRNAs, implying that our understanding of lncRNA transcriptional regulation is incomplete. Here, we perform an in depth characterization of numerous factors contributing to this regulation. We find that lncRNA promoters contain fewer transcription factor binding sites than do those of mRNAs, with some notable exceptions. Surprisingly, we find that H3K9me3 –typically associated with transcriptional repression–is enriched at active lncRNA loci. However, the most discriminant differences between lncRNAs and mRNAs involve splicing: only half of lncRNAs are efficiently spliced, which can be partially attributed to defects in lncRNA splicing signals and diminished U2AF65 binding. These attributes are conserved between humans and mice. Finally, we find that certain transcriptional properties are enriched in known, functionally characterized lncRNAs, demonstrating that our multidimensional analysis might discern lncRNAs that are likely to be functional Overall design: Examination of RNA abundance in two cell lines (K562 and Hues9) and 5 time points after actinomycin D treatment. Three replicates per time point and cell type.
Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs.
Cell line, Subject, Time
View SamplesSpinal muscular atrophy (SMA) is one of the most common inherited forms of neurological disease leading to infant mortality. Patients exhibit selective loss of lower motor neurons resulting in muscle weakness, paralysis, and often death. Although patient fibroblasts have been used extensively to study SMA, motor neurons have a unique anatomy and physiology which may underlie their vulnerability to the disease process. Here we report the generation of induced pluripotent stem (iPS) cells from skin fibroblast samples taken from a child with SMA. These cells expanded robustly in culture, maintained the disease genotype, and generated motor neurons that showed selective deficits compared to those derived from the childs unaffected mother. This is the first study to show human iPS cells can be used to model the specific pathology seen in a genetically inherited disease. As such, it represents a promising resource to study disease mechanisms, screen novel drug compounds, and develop new therapies.
Induced pluripotent stem cells from a spinal muscular atrophy patient.
No sample metadata fields
View SamplesFK1706 potentiated nerve growth factor-induced neurite outgrowth, putatively mediated via FKBP-52 and the Ras/Raf/MAPK signaling pathway. It also improved mechanical allodynia accompanied by the recovery of intraepidermal nerve fiber density in a painful diabetic neuropathy in rats.
FK1706, a novel non-immunosuppressive immunophilin ligand, modifies gene expression in the dorsal root ganglia during painful diabetic neuropathy.
Specimen part, Treatment
View SamplesThe significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury. Overall design: We generated transciptome data from proliferative cardiac cells collected from 3, 7 or 14 days following myocardial infarction (MI) or sham surgery. This series includes single-cell transcriptome data from (Ki67-RFP+) cardiac cells collected from neonatal murine hearts, adult homeostatic murine hearts or adult murine hearts collected 14 days following myocardial infarction (MI), ischemic/perfusion (I/R) or sham surgery.
Profiling proliferative cells and their progeny in damaged murine hearts.
Specimen part, Subject, Time
View SamplesScope: As a result of population ageing, the number of Alzheimer’s disease (AD) patients has rapidly increased. There are many hypothesises on the pathogenesis of AD, but its detailed molecular mechanism is still unknown, and so no effective preventive or therapeutic measures have been established. Some reports showed a decrease in levels of norepinephrine (NE) has been suspected to be involved in the decline of cognitive function in AD patients and NE concentrations were decreased in postmortem AD patient brains. Tyr-Trp was identified as being the most effective dipeptide in enhancing norepinephrine (NE) synthesis and metabolism. And Tyr-Trp treatment ameliorated the short-term memory dysfunction in AD model mice caused by amyloid beta (Aβ) 25-35. So, the purpose of this study was to investigate the preventive or/and protective effects of Tyr-Trp administration in AD model mice.
Tyr-Trp administration facilitates brain norepinephrine metabolism and ameliorates a short-term memory deficit in a mouse model of Alzheimer's disease.
Specimen part
View SamplesOBF1, also known as Bob.1 or OCA-B, is a B lymphocyte-specific transcription factor which coactivates Oct1 and Oct2 on B cell specific promoters. So far, the function of OBF1 has been mainly identified in late stage B cell populations. The central defect of OBF1 deficient mice is a severely reduced immune response to T cell-dependent antigens and a lack of germinal center formation in the spleen. Relatively little is known about a potential function of OBF1 in developing B cells. Here we have generated transgenic mice overexpressing OBF1 in B cells under the control of the immunoglobulin heavy chain promoter and enhancer. Surprisingly, these mice have greatly reduced numbers of follicular B cells in the periphery and have a compromised immune response. Furthermore, B cell differentiation is impaired at an early stage in the bone marrow. A first block is observed during B cell commitment and a second differentiation block is seen at the large preB2 cell stage. The cells that succeed to escape the block and to differentiate into mature B cells have post-translationally downregulated the expression of transgene, indicating that expression of OBF1 beyond the normal level early in B cell development is deleterious. Indeed ID3, which is a negative regulator of B cell differentiation, is upregulated in the EPLM and preB cells of the transgenic mice. Furthermore ID3 promoter contains an octamer site suggesting that it is a potential OBF-1 direct target gene. These results provide evidence that OBF1 expression has to be tightly regulated in early B cells to allow efficient B lymphocyte differentiation.
Enforced expression of the transcriptional coactivator OBF1 impairs B cell differentiation at the earliest stage of development.
No sample metadata fields
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