The main cell of origin of the Sonic hedgehog (SHH) subgroup of medulloblastoma (MB) is granule cell precursors (GCPs), a SHH-dependent transient amplifying population in the developing cerebellum. SHH-MBs can be further subdivided based on molecular and clinical parameters, as well as location since SHH-MBs occur preferentially in the lateral cerebellum (hemispheres). Our analysis of adult patient data suggests that tumors with Smoothened (SMO) mutations form more specifically in the hemispheres than those with Patched 1 (PTCH1) mutations. Using sporadic mouse models of SHH-MB with the two mutations commonly seen in adult MB, constitutive activation of Smo (SmoM2) or loss-of-Ptch1, we found that regardless of timing of induction or type of mutation, tumors developed primarily in the hemispheres with SmoM2-mutants indeed showing a stronger specificity. We further uncovered that GCPs in the hemispheres are more susceptible to high level SHH signaling compared to GCPs in the medial cerebellum (vermis), as more SmoM2 or Ptch1-mutant hemisphere cells remain undifferentiated and show increased tumorigenicity when transplanted. Finally, we identified location-specific GCP gene expression profiles, and found that deletion of the genes most highly expressed in the hemispheres (Nr2f2) or vermis (Engrailed1) showed opposing effects on GCP differentiation. Our studies thus provide new insights into intrinsic differences within GCPs that impact on SHH-MB progression.
Lateral cerebellum is preferentially sensitive to high sonic hedgehog signaling and medulloblastoma formation.
Specimen part
View SamplesWe studied the changes that occur in gene transcription during seasonal senescence in Populus trichocarpa pioneer leaves and fine roots. Plant senescence is a strictly regulated physiological process that allows relocating of valuable nutrients from senescent tissues before death. It might be induced by internal or external factors and among them, phytohormones play an undoubtedly significant role. Senescence was extensively studied in leaves, but the aging of other ephemeral organs, located underground, and its drivers are still poorly understood. We focused on collective results to fill in the knowledge gap about senescence of fine, absorptive roots and leaves in order to check if there are universal mechanisms involved during plant organ senescence. Transcriptional profiling was conducted with the use of microarrays to identify genes involved in developmental PCD. Samples were collected three times during a growth season. The first collection was considered as a control and was collected in early summer (July 7–15) when leaves and the root system were fully developed and functional. The second group of leaf and root samples were harvested in early autumn (October 1–7) when chlorophyll levels in leaves had decreased by approximately 40% and when fine roots had changed in color from white to brown. The third group of samples were harvested in the middle of autumn (November 2–9) when chlorophyll levels in leaves decreased by approximately 65% and fine roots were dark brown or black color. Our results reveal the important role of phytohormones in regulating the senescence of both studied organs. The transcriptomic analyses showed significant changes in gene expression that are associated with phytohormones, especially with ABA and jasmonates. We conclude that phytohormonal regulation of senescence in roots and leaves is organ-specific. In roots, phytohormones are involved indirectly in regulation of senescence by increasing tolerance for cold or resistance for pathogens, whereas such correlation was not observed in leaves.
Allies or Enemies: The Role of Reactive Oxygen Species in Developmental Processes of Black Cottonwood (<i>Populus trichocarpa</i>).
Specimen part
View SamplesThe purpose of this study was to deteremine gene expression changes in when HMCES is inactivated. We found very few changes. Overall design: Compare wild type and HMCES knockout U2OS cancer cells using RNA-seq.
HMCES Maintains Genome Integrity by Shielding Abasic Sites in Single-Strand DNA.
Specimen part, Cell line, Subject
View SamplesThis study was designed to define erythropoietin (EPO) regulated genes in murine bone marrow erythroid progenitor cells at two stages of development, designated E1, and E2. E1 cells correspond to CFUe- like progenitors, while E2 cells are proerythroblasts.
Defining an EPOR- regulated transcriptome for primary progenitors, including Tnfr-sf13c as a novel mediator of EPO- dependent erythroblast formation.
Sex, Specimen part, Treatment
View SamplesThe aim of this study was to explore what molecular and cellular processes predicate the conversion from insulitis to diabetes. The transcriptional profiles of CD45+ immune cells collected from pancreas of a cohort of age-matched female mice, which were scanned by MRI to determine the risk of diabetes development.
Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging.
Sex, Age, Specimen part
View SamplesGene expression was compared between E18.5 E-cadherin conditional knockout (cKO) small intestine and E18.5 control mouse small intestine.
E-cadherin is required for intestinal morphogenesis in the mouse.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The transcriptional coregulator MAML1 affects DNA methylation and gene expression patterns in human embryonic kidney cells.
Cell line, Treatment
View SamplesMastermind-like 1 (MAML1) is a transcriptional coregulator that has been associated with early development of many systems such as neuronal, muscular, cardiovascular and urogenital. The present study aimed to explore the genome-wide effects of MAML1 on gene expression and DNA methylation in human embryonic kidney cells. RNA expression was measured using a microarray that screens approximately 36,000 transcripts, and DNA methylation was determined for 450,000 CpG sites. 225 genes were found to be differentially expressed, while 11802 CpG sites were found to be differentially methylated in MAML1-expressing cells. A subset of 211 differentially methylated loci was associated with the expression of 85 genes. Gene ontology analysis revealed that these genes are involved in the regulation of urogenital system development, cell adhesion and embryogenesis.
The transcriptional coregulator MAML1 affects DNA methylation and gene expression patterns in human embryonic kidney cells.
Cell line, Treatment
View SamplesHTETOP cells, derived from the human fibrosarcoma cell line HT1080, express human topoisomearse II (TOP2A) exclusively from a tetracycline (TET)-regulated transgene, we used HTETOP cells to differentiate between TOP2A-dependent and independent apoptotic effects of doxorubicin and dexrazoxane.
Topoisomerase II{alpha}-dependent and -independent apoptotic effects of dexrazoxane and doxorubicin.
Cell line
View SamplesIn order to understand the effect of genetic background on the response to gene dose perturbation, we performed mRNA transcriptional profiling on 99 hemizygotic lines (Df/+) from the DrosDel project, which have hybrid genetic background of OregonR/w1118. Overall design: We performed RNA-Seq analysis of 417 single adult flies in duplicate or triplicate. Flies are from 73 different genotypes. Differential gene expression was analyzed separately for each sex, gene expression from each genotype was compared to normalized mean of gene expression remaining 72 genotypes.
Dosage-Dependent Expression Variation Suppressed on the <i>Drosophila</i> Male <i>X</i> Chromosome.
Sex, Subject
View Samples