Recurrent Copy Number Variations (CNVs) of human 16p11.2 have been associated with a variety of developmental/neurocognitive syndromes. In particular, deletion of 16p11.2 is found in patients with autism, developmental delay, and obesity. Patients with deletions or duplications have a wide range of clinical features, and siblings carrying the same deletion often have diverse symptoms. To study the consequence of 16p11.2 CNVs in a systematic manner, we used chromosome engineering to generate mice harboring deletion of the chromosomal region corresponding to 16p11.2, as well as mice harboring the reciprocal duplication. These 16p11.2 CNV models have dosage-dependent changes in gene expression, viability, brain architecture, and behavior. For each phenotype, the consequence of the deletion is more severe than that of the duplication. Of particular note is that half of the 16p11.2 deletion mice die postnatally; those that survive to adulthood are healthy and fertile, but have alterations in the hypothalamus and exhibit a behavior trap phenotypea specific behavior characteristic of rodents with lateral hypothalamic and nigrostriatal lesions. Our findings indicate that 16p11.2 CNVs cause both brain and behavioral anomalies, providing new insight into human neurodevelopmental disorders.
Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism.
Sex
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Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Specimen part, Cell line, Treatment
View SamplesOur study in zebrafish is the first to use an animal model to understand the biology of the developmental disorder Roberts Syndrome (RBS). RBS is caused by mutations in the ESCO2 gene.
A zebrafish model of Roberts syndrome reveals that Esco2 depletion interferes with development by disrupting the cell cycle.
Age, Specimen part
View SamplesTo further understand the differences occurring in MCF10A cells as they polarize and differentiate in the Transwell model, we performed gene expression profiling with Affymetrix Human Genome U133 Plus 2.0 Arrays. Four experimental time points, were sampled: conventional cultures of MCF10A cells grown on plastic (Monolayer) and MCF10A cells plated on Transwells sampled at three TEER values, 200-300 cm2 (Base), 1400-1600 cm2 (Midpoint), and 3000-3200 cm2 (Plateau).
In vitro multipotent differentiation and barrier function of a human mammary epithelium.
No sample metadata fields
View SamplesWe compared TET1 and TET3 overexpressing cells to uninduced cells with endogenous levels of the respective transcript to determine global gene expression changes.
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Specimen part, Treatment
View SamplesWe initiated a study to investigate the transcriptional profiles associated with cell states of the stomatal lineage. A stem-cell like precursor of stomata, a meristemoid. reiterates asymmetric divisions and renews itself before differentiating into guard cells. The transient and asynchronous nature of the meristemoid has made it difficult to study its molecular characteristics. Through combinatorial use of genetic resources that either arrest or constitutively drive stomatal cell-state progressions due to loss- or gain-of-function mutations in the key transcription factor genes, SPEECHLESS, MUTE, and SCRM, we obtained seedlings highly enriched in pavement cells, meristemoids, or stomata. Here we present transcriptome and genome-wide trends in gene regulation associated with each cell state and identify molecular signatures associated with meristemoids.
Molecular profiling of stomatal meristemoids reveals new component of asymmetric cell division and commonalities among stem cell populations in Arabidopsis.
Age, Specimen part
View SamplesWe report that increased nutrient availability increases breeding success and egg production. RNA-seq analysis revealed that parental diet altered the expression of metabolic genes in the unfertilized eggs. Offspring from the differentially fed parents showed altered survival and energy expenditure as adults. Overall design: RNA from unfertilized eggs after two parental diets.
Dietary Intake Influences Adult Fertility and Offspring Fitness in Zebrafish.
No sample metadata fields
View SamplesWe compared TET triple knockdown cells to control cells treated with non-targeting siRNAs to determine global gene expression changes.
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Cell line, Treatment
View SamplesBackground: Genes upregulated by low oxygen have been suggested as endogenous markers for tumor hypoxia. Yet, most of the genes investigated have shown inconsistent results, which have led to concerns about their ability to be true hypoxia markers. Previous studies have demonstrated that expression of hypoxia induced genes can be affected by extracellular pH (pH e ). Methods: Five different human cell lines (SiHa, FaDu DD, UTSCC5, UTSCC14 and UTSCC15) were exposed to different oxygen concentrations and pH (7.5 or 6.3), and gene expression analyzed with microarray (Affymetrix - Human Genome U133 Plus 2.0 Array). Results: An analysis of two of the cell lines using SAM identified 461 probesets that were able to separate the four groups Normal oxygen, normal pH , Low oxygen, normal pH , Normal oxygen, low pH and Low oxygen, low pH . From here it was possible to identify a fraction of probesets induced at low oxygen independent of pH in these two cell lines, this fraction included HIG2, NDRG1, PAI1 and RORA. Further verifi cation by qPCR highlighted the necessity of using more cell lines to obtain a robust gene expression profi les. To specifi cally select pH independent hypoxia regulated genes across more cell lines, data for FaDu DD, UTSCC5, UTSCC14 and UTSCC15 were analyzed to identify genes that were induced by hypoxia in each cell line, where the induction was not affected by low pH, and where the gene was not signifi cantly induced by low pH alone. Each cell line had 65 122 probesets meeting these criteria. For genes to be considered as target genes (hypoxia inducible pH independent), genes had to be present in three of four cell lines. Conclusion: The result is a robust hypoxia profile unaffected by pH across cell lines consisting of 27 genes. This study demonstrates a way to identify hypoxia markers by microarray, where other factors in the tumor microenvironment are taken into account.
Identifying pH independent hypoxia induced genes in human squamous cell carcinomas in vitro.
Cell line
View SamplesRetinitis pigmentosa (RP) is a photoreceptor disease that affects approximately 100,000 people in the United States. There are currently very limited treatment options and the prognosis for most patients is progressive vision loss. Unfortunately, the understanding of the molecular underpinnings of RP initiation and progression is still poorly understood. However, the development of animal models of RP, coupled with high-throughput sequencing, has provided an opportunity to study the underlying cellular and molecular changes of this disease. Using RNA-Seq, we present the first retinal transcriptome analysis of the rd10 murine model of retinal degeneration. Overall design: RNA-Seq on whole-retina samples from rd10, wild-type and GFP-expressing mouse retina. Three biological replicates of each.
A profile of transcriptomic changes in the rd10 mouse model of retinitis pigmentosa.
No sample metadata fields
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