It is generally believed that cerebellar granule neurons originate exclusively from granule neuron precursors (GNPs) in the external germinal layer (EGL). Here we identify a rare population of neuronal progenitors in the developing cerebellum that expresses Nestin. Although Nestin is widely considered a marker for multipotent stem cells, these Nestin-expressing progenitors (NEPs) are committed to the granule neuron lineage. Unlike conventional GNPs, which reside in the outer EGL and proliferate extensively, NEPs reside in the deep part of the EGL and are quiescent. Expression profiling reveals that NEPs are distinct from GNPs, and in particular, express markedly reduced levels of genes associated with DNA repair. Consistent with this, upon aberrant activation of Sonic hedgehog (Shh) signaling, NEPs exhibit more severe genomic instability and give rise to tumors more efficiently than GNPs. These studies identify a novel progenitor for cerebellar granule neurons and a novel cell of origin for medulloblastoma.
A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity.
Specimen part
View SamplesEpithelial gland development within the uterine lining during prepubertal period is important to ensure successful gestation in adults. Lgr5 expression in uterus becomes largely restricted to the tips of developing glands after birth. These Lgr5 highly expressing cells function as stem cells during gland development.
Neonatal Wnt-dependent Lgr5 positive stem cells are essential for uterine gland development.
Specimen part
View SamplesTH-MYCN transgenic (Tg) mice are the model for neuroblastoma. One of the sympathetic ganglia is the origin of neuroblastoma in those mice. The tumor incidences of homozygotes and hemizygotes are 100% and 70-80%, respectively.
Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells.
Specimen part
View SamplesAML/MDS patients carrying 11q amplifications involving the mixed lineage leukemia gene (MLL) locus are characterized by a later onset, a complex aberrant karyotype (CAK) frequently including deletions within 5q, 17p and 7q, as well as fast progression of the disease with extremely poor prognosis. We and other have shown that the MLL gene is over expressed in amplified cases, however, in most of the cases the amplified region is not restricted to the MLL locus. In the present study we investigated 19 patients with AML/MDS and MLL gain/amplification [15 AML (two secondary, following MDS and PV, and three therapy related) and 4 MDS cases (two therapy related)]. By means of array CGH performed in 12 patients (GSE9928) we were able to delineate the minimal deleted regions within 5q, 17p and 7q and identified three independent regions 11q/I-III that were amplified in all cases. Gene expression profiles established in 15 cases were used to define the candidate genes within these regions. Interestingly, analysis of our data suggests an interdependency of genes influenced by losses of 5q and 17p and expression of genes present in 11q23-25. Additionally, we demonstrate that the gene expression signature can be used to discriminate AML/MDS with MLL amplification from all other types of AML, thus, indicating specific pathogenesis present in this entity.
AML/MDS with 11q/MLL amplification show characteristic gene expression signature and interplay of DNA copy number changes.
Sex, Age, Specimen part, Disease
View SamplesTo examine irreversible changes in the developing brain following seizures, juvenile inbred mice were intraperitoneally injected with kainate and nicotine.
Increased expression of the lysosomal protease cathepsin S in hippocampal microglia following kainate-induced seizures.
No sample metadata fields
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 SamplesPaf1 and Ski8 were selected as representative subunits of the Paf1 complex (PAF1C), and RNA-seq analysis was performed in triplicate to compare the genes affected by Paf1, Ski8, and Rtf1 knockdown in HeLa cells. Overall design: Total RNA was harvested from control HeLa and Ski8 knockdown cells at day 4 and from Rtf1 or Paf1 knockdown cells at day 7 and was subjected to RNA-seq in triplicates.
Correction for Cao et al., Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex.
No sample metadata fields
View SamplesAltered gene expression in the sphingosine 1-phosphate receptor 2 (S1P2)-deficient or sphingosine 1-phosphate receptor 3 (S1P3)-deficient brain.
Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2.
No sample metadata fields
View SamplesDuring seed maturation, the embryo accumulates nutrition storage compounds such as oil and reservve proteins, and acquires dormancy and desiccation tolerance. Arabidopsis transcription factors LEC1, LEC2, FUS3 and ABI3 are known as the master regulators of seed maturation because all these events during the seed maturation are severely affected by the respective mutants. In addition, the lec1, lec2 and fus3 mutants exhibit some heterochronic characteristics, as exemplified by the development of true leaf-like cotyledons during embryogenesis. To characterize these mutants at the whole genome expression level, microarray experiments were performed.
Cell-by-cell developmental transition from embryo to post-germination phase revealed by heterochronic gene expression and ER-body formation in Arabidopsis leafy cotyledon mutants.
Specimen part
View SamplesAlthough gain of chromosome-5p is one of the most frequent DNA copy number imbalances in cervical squamous cell carcinoma (SCC), the genes that drive its selection remain poorly understood. In a previous cross-sectional clinical study we showed that the microRNA processor Drosha (located on chromosome-5p) demonstrates frequent copy-number gain and over-expression in cervical SCC, associated with altered microRNA profiles. Here, we have conducted gene depletion/over-expression experiments to demonstrate the functional significance of up-regulated Drosha in cervical SCC cells. Drosha depletion by RNA-interference (RNAi) produced significant, specific reductions in cell motility/invasiveness in vitro, with a silent RNAi-resistant Drosha mutation providing phenotype rescue. Unsupervised hierarchical clustering following global profiling of 319 microRNAs in eighteen cervical SCC cell line specimens generated two groups according to Drosha expression levels. Altering Drosha levels in individual SCC lines changed the group into which the cells clustered, with gene depletion effects being rescued by the RNAi-resistant mutation. Forty-five microRNAs showed significant differential expression between the groups, including four of fourteen that were differentially-expressed in association with Drosha levels in clinical samples. miR-31 up-regulation in Drosha over-expressing samples/cell lines was the highest-ranked change (by adjusted p-value) in both analyses, an observation validated by Northern blotting. These functional data support the role of Drosha as an oncogene in cervical SCC, by affecting expression of cancer-associated microRNAs that have the potential to regulate numerous protein-coding genes.
Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles.
Sex, Cell line
View Samples