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GSE54294
Rattus norvegicus
24 Downloadable Samples
Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Bone development and regeneration is associated with the Wnt signaling pathway that, according to literature, can be modulated by lithium ions (Li+). The aim of this study was to evaluate the gene expression profile during peri-implant healing of poly(lactic-co-glycolic acid) (PLGA) implants with incorporated Li+, while PLGA without Li+ was used as control, and a special attention was then paid to the Wnt signaling pathway. The implants were inserted in rat tibia for 7 or 28 days and the gene expression profile was investigated using a genome-wide microarray analysis. The results were verified by qPCR and immunohistochemistry. Histomorphometry was used to evaluate the possible effect of Li+ on bone regeneration. The microarray analysis revealed a large number of significantly differentially regulated genes over time within the two implant groups. The Wnt signaling pathway was significantly affected by Li+, with approximately 34% of all Wnt-related markers regulated over time, compared to 22% for non-Li+ containing (control; Ctrl) implants. Functional cluster analysis indicated skeletal system morphogenesis, cartilage development and condensation as related to Li+. The downstream Wnt target gene, FOSL1, and the extracellular protein-encoding gene, ASPN, were significantly upregulated by Li+ compared with Ctrl. The presence of -catenin, FOSL1 and ASPN positive cells was confirmed around implants of both groups. Interestingly, a significantly reduced bone area was observed over time around both implant groups. The presence of periostin and calcitonin receptor-positive cells was observed at both time points. This study is to the best of the authors knowledge the first report evaluating the effect of a local release of Li+ from PLGA at the fracture site. The present study shows that during the current time frame and with the present dose of Li+ in PLGA implants, Li+ is not an enhancer of early bone growth, although it affects the Wnt signaling pathway.
Publication Title
Gene expression profiling of peri-implant healing of PLGA-Li+ implants suggests an activated Wnt signaling pathway in vivo.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Targets of Retinoic Acid (RA) and 3,4-didehydroretinoic acid (ddRA) were identified in primary human epidermal keratinocytes grown in the presence of atRA or ddRA for 4 and 24 hours.
Publication Title
The effect of two endogenous retinoids on the mRNA expression profile in human primary keratinocytes, focusing on genes causing autosomal recessive congenital ichthyosis.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Amplification of large chromosomal regions (gene amplification) is a common somatic alteration in human cancer cells and often is associated with advanced disease. A critical event initiating gene amplification is a DNA double strand break (DSB), which is immediately followed by the formation of a large DNA palindrome. Large DNA palindromes are frequent and non-randomly distributed in the genomes of cancer cells and facilitate further increase in copy number. Although the importance of the formation of large DNA palindromes as a very early event in gene amplification is widely recognized, it is not known 1) how a DSB is resolved to form a large DNA palindrome; and 2) whether any local DNA structure determines the location of large DNA palindromes. We show here that intra-strand annealing following a DNA double-strand break leads to the formation of large DNA palindromes and that DNA inverted repeats in the genome determines the efficiency of this event. Furthermore, in human Colo320DM cancer cells, a DNA inverted repeat in the genome marks the border between amplified and non-amplified DNA. Therefore, an early step of gene amplification is a regulated process that is facilitated by DNA inverted repeats in the genome.
Publication Title
Intrastrand annealing leads to the formation of a large DNA palindrome and determines the boundaries of genomic amplification in human cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
NextSeq 500
Description
Long-term maintenance of spermatogenesis in mammals is supported by GDNF, an essential growth factor required for spermatogonial stem cell (SSC) self-renewal. Exploiting a transgenic GDNF overexpression model, which expands and normalizes the pool of undifferentiated spermatogonia between Plzf +/+ and Plzf lu/lu mice, we used RNAseq to identify a rare subpopulation of cells that express EOMES, a T-box transcription factor. Lineage tracing, conditional ablation, and busulfan challenge show that these are long-term SSCs that contribute to steady state spermatogenesis as well as regeneration following chemical injury. EOMES+ SSCs have a lower proliferation index than EOMES- GFRA1+ spermatogonia in wild-type but not in Plzf lu/lu mice. This comparison demonstrates that PLZF regulates their proliferative activity and suggests that EOMES+ SSCs are lost through proliferative exhaustion in Plzf lu/lu mice. Single cell RNA sequencing of EOMES+ cells from Plzf +/+ and Plzf lu/lu mice support a hierarchical model of a slow-cycling long-term SSC population supporting more rapid-cycling short-term SSCs. Overall design: 384-well plate-based 3'-end scRNA-seq was performed on two groups, Plzf +/+ and Plzf lu/lu, of cells across 4 plates. Plzf +/+ cells were spread across 2 plates and Plzf lu/lu cells were spread over 1 plate. The 4th plate contains both Plzf lu/lu (up to well C15) and Plzf +/+ (well C15 onward). Each sample in this record represents one plate.
Publication Title
Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
shRNA-mediated ablation of the RING-finger protein TRIM52 from multiple glioblastoma cell lines reduces proliferation and tumorigenesis. To identify gene signatures underlying this phenomenon, transcritional profile of TRIM52 knockdown cells was compared to control cells. Upon TRIM52 ablation, we find 278 differentially regulated genes. Gene ontology analysis reveals that many of the upregulated genes are associated with glycolysis and biosynthetic processes. Overall design: U87MG glioblastoma cells were stably transduced with doxycycline-inducible shRNA constructs targeting TRIM52 (two different shRNAs) or controls (two different non-targeting shRNAs). Knockdown was induced for five days using 2µg/ml doxycycline. shRNA expressing cells were sorted based on shRNA-coupled GFP expression via flow cytometry. mRNA sequening was performed in duplicate per shRNA cell line.
Publication Title
Human tripartite motif protein 52 is required for cell context-dependent proliferation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 146 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 146 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Intra-tumor heterogeneity is a hallmark of glioblastoma multiforme, and thought to negatively affect treatment efficacy. Here we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability between clones, including a wide range of responses to radiation and drugs. This widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-to-mesenchymal shift in the transcriptome.
Publication Title
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Steroid hormones regulate essential physiological processes and inadequate levels are associated with various pathological conditions. In testosterone-producing Leydig cells, steroidogenesis is strongly stimulated by LH via its receptor leading to increased cAMP production and expression of the steroidogenic acute regulatory (STAR) protein, which is essential for the initiation of steroidogenesis. Leydig cell steroidogenesis then passively decreases following the rapid degradation of cAMP into AMP by phosphodiesterases. In this study, we show that AMP-activated protein kinase (AMPK) is activated following cAMP breakdown in MA-10 and MLTC-1 Leydig cells. Activated AMPK then actively inhibits cAMP-induced steroidogenesis by repressing the expression of key regulators of steroidogenesis including Star and Nr4a1. Similar results were obtained in Y-1 adrenal cells and in the constitutive steroidogenic cell line R2C. Our data identify AMPK as an active repressor of steroid hormone biosynthesis in steroidogenic cells that is essential to preserve cellular energy and prevent excess steroid production.
Publication Title
A cell-autonomous molecular cascade initiated by AMP-activated protein kinase represses steroidogenesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- NextSeq 550
Description
We obtained single-cell RNA-sequencing (scRNA-seq) profiles of CD14+ monocytes isolated from human peripheral blood at 0, 3 and 6 days after M-CSF stimulation (to differentiate the cells into macrophages) across multiple donors. Integration of single-cell RNA sequencing (scRNA-seq) data from multiple experiments, laboratories, and technologies can uncover biological insights, but current methods for scRNA-seq data integration are limited by a requirement for datasets to derive from functionally similar cells. We use a novel algorithm, Scanorama, to identify and merge the shared cell types among all pairs of datasets and to accurately integrate heterogeneous scRNA-seq datasets. Scanorama is sensitive to subtle temporal changes within the same cell lineage, successfully integrating functionally similar cells across time series data of CD14+ monocytes at different stages of differentiation into macrophages. Scanorama is not only able to differentiate between completely disparate cell types but is also sensitive to subtler transcriptional changes within a cell type due to processes like stimulation. Overall design: scRNA-seq of human CD14+ monocytes at 0, 3, and 6 days after M-CSF stimulation in multiple donors
Publication Title
Efficient integration of heterogeneous single-cell transcriptomes using Scanorama.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Disruption of N-linked glycosylation has a broad impact on proper glycosylation of nascent glycoproteins in the endoplasmic reticulum, which affect multiple signalling pathways( by changing the stability of membrane proteins or the signalling ability of membrane receptors) and may be responsible of the fibrotic stage associated to CDG type-I.
Publication Title
Fibrotic response in fibroblasts from congenital disorders of glycosylation.
Sample Metadata Fields
No sample metadata fields
View Samples