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GSE32398
Homo sapiens
13 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Comparison of human prepuberal articular and growth plate cartilage
Publication Title
Gremlin 1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human aging is associated with loss of function and regenerative capacity. Human bone marrow derived mesenchymal stromal cells (hMSCs) are involved in tissue regeneration, evidenced by their capacity to differentiate into several lineages and therefore are considered the gold standard for cell-based regeneration therapy. Tissue maintenance and regeneration is dependent on stem cells and declines with age and aging is thought to influence therapeutic efficacy, therefore, more insight in the process of aging of hMSCs is of high interest. We, therefore, hypothesized that hMSCs might reflect signs of aging. In order to find markers for donor age, early passage hMSCs were isolated from bone marrow of 61 donors, with ages varying from 17-84, and clinical parameters, in vitro characteristics and microarray analysis were assessed. Although clinical parameters and in vitro performance did not yield reliable markers for aging since large donor variations were present, genome-wide microarray analysis resulted in a considerable list of genes correlating with human age. By comparing the transcriptional profile of aging in human with the one from rat, we discovered follistatin as a common marker for aging in both species. The gene signature presented here could be a useful tool for drug testing to rejuvenate hMSCs or for the selection of more potent, hMSCs for cell-based therapy.
Publication Title
A mesenchymal stromal cell gene signature for donor age.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 53 Downloadable Samples
IlluminaHiSeq2000
Description
Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS cases (8,224 AS, 1,437 APA), including changes in ALS-associated genes (e.g. ATXN2 and FUS), and cases of sporadic ALS (sALS; 2,229 AS, 716 APA). Furthermore, hnRNPH and other RNA-binding proteins are predicted as potential regulators of cassette exon AS events for both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS. Overall design: Examination transcriptiome profiles in c9orf72-associated ALS, sporadic ALS and healthy control
Publication Title
Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Wnt signaling potentiates nevogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Melanocytes within benign human nevi are the paradigm for tumor suppressive senescent cells in a pre-malignant neoplasm. These cells typically contain mutations in either the BRAF or N-RAS oncogene and express markers of senescence, including p16. However, a nevus can contain 10s to 100s of thousands of clonal melanocytes and approximately 20-30% of melanoma are thought to arise in association with a pre-existing nevus. Neither observation is indicative of fail-safe senescence-associated proliferation arrest and tumor suppression. We set out to better understand the status of nevus melanocytes. Proliferation-promoting Wnt target genes, such as cyclin D1 and c-myc, were repressed in oncogene-induced senescent melanocytes in vitro, and repression of Wnt signaling in these cells induced a senescent-like state. In contrast, cyclin D1 and c-myc were expressed in many melanocytes of human benign nevi. Specifically, activated Wnt signalling in nevi correlated inversely with nevus maturation, an established dermatopathological correlate of clinical benignancy. Single cell analyses of lone epidermal melanocytes and nevus melanocytes showed that expression of proliferation-promoting Wnt targets correlates with prior proliferative expansion of p16-expressing nevus melanocytes. In a mouse model, activation of Wnt signaling delayed, but did not bypass, senescence of oncogene-expressing melanocytes, leading to massive accumulation of proliferation-arrested, p16-positive non-malignant melanocytes. We conclude that clonal hyperproliferation of oncogene-expressing melanocytes to form a nevus is facilitated by transient delay of senescence due to activated Wnt signaling. The observation that activation of Wnt signaling correlates inversely with nevus maturation, an indicator of clinical benignancy, supports the notion that persistent destabilization of senescence by Wnt signaling contributes to the malignant potential of nevi.
Publication Title
Wnt signaling potentiates nevogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
OIS is characterized by a stable proliferation arrest and secretion of pro-inflammatory cytokines and chemokines, the senescence-associated secretory phenotype (SASP). Proliferation arrest and the SASP collaborate to enact tumor suppression, the former by blocking cell proliferation and the latter by recruiting immune cells to clear damaged cells. However, the interactions of OIS cells with the immune system are still poorly defined. Here we show that engagement of OIS in primary human melanocytes, specifically by melanoma driver mutations NRASQ61K and BRAFV600E, causes expression of the MHC class II antigen presentation apparatus, via secreted IL1ß signaling and expression of CIITA, a master regulator of MHC class II gene transcription. Overall design: We quantify transcription via high throughput RNA sequencing in nevus melanocytes in cross FVB/NJ mice with Cre inducible NRAS61K with an MHCII cross
Publication Title
Oncogene-Expressing Senescent Melanocytes Up-Regulate MHC Class II, a Candidate Melanoma Suppressor Function.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 4000
Description
Human T-lymphotropic virus type 1 (HTLV-1) is associated with the development of Adult T-cell Leukemia, an aggressive CD4+ T-cells malignancy. Here, we have developed a new procedure to infect humanized mice with proviruses displaying specific mutations, such as one leading to the loss of the PDZ domain-binding motif (PBM) of Tax. In order to specifically analyze the in vivo role of the PBM of Tax, a comparative study of infected hu-mice was performed. We used next-generation sequencing to perform genome-wide transcriptomic analysis of T-cells infected with wild-type HTLV-1 virus or with virus bearing a mutated form of Tax lacking the PBM. Our results suggest that Tax PBM might be involved in the regulation of genes implicated in proliferation, apoptosis and cytoskeleton organization. Overall design: mRNA profiles of T-cells obtained from hu-Mice infected with wild-type or Tax-PBM HTLV-1 were generated by deep-sequencing in triplicates using Illumina's Hiseq3000 platform.
Publication Title
PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- NextSeq500
Description
Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signalling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here we show that multinucleate OIS cells originated mostly from failed mitosis. Prior to senescence, mutant RasV12 activation in primary human fibroblasts compromised mitosis, associated with abnormal expression of mitotic genes that enter M-phase. Simultaneously, RasV12 activation enhanced survival of damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional up-regulation of Mcl1 was responsible for enhanced slippage of cells with mitotic defects and subsequent cell survival. Importantly, mitotic slippage and oncogene signalling synergistically induced senescence and key senescence regulators p21 and p16. We propose that activated Ras induces transcriptional changes that predispose cells undergoing OIS to mitotic stress and multinucleation. Overall design: We used RNA-seq of IMR90 cells with inducible expression of oncogenic RasV12 that were synchronised in mitosis, to characterise the nature of mitotic defects that lead to multinucleation of oncogene-induced senescent cells
Publication Title
Mitotic Stress Is an Integral Part of the Oncogene-Induced Senescence Program that Promotes Multinucleation and Cell Cycle Arrest.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
LncRNA H19X was silienced in dermal fibroblats of systemic sclerosis patients with antisense oligonuclotides. The hypothesis tested in the present study was that H19X is an important factor in the development of TGFb-driven fibrosis. Results provide important information about the role H19X in fibroblasts in particolar on extracellular matrix production and cell cycle regulation.
Publication Title
Long noncoding RNA H19X is a key mediator of TGF-β-driven fibrosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Glucocorticoids are a well recognized and common cause of muscle atrophy. Glucocorticoid-induced atrophy can be prevented by testosterone, but the molecular mechanisms underlying such protection have not been described. Thus, the global effects of testosterone on dexamethasone-induced changes in gene expression were evaluated in rat gastrocnemius muscle using Affymetrix 230_2 DNA microarrays. Gene expression was analyzed after 7 days administration of dexamethasone, dexamethasone plus testosterone, or vehicle. Effects of these agents on weights of gastrocnemius muscles from these animals has been reported (1. Zhao W, Pan J, Zhao Z, Wu Y, Bauman WA, and Cardozo CP. Testosterone protects against dexamethasone-induced muscle atrophy, protein degradation and MAFbx upregulation. J Steroid Biochem Mol Biol 110: 125-129, 2008.) Dexamethasone changed expression of 876 probe sets by at least 2-fold, of which 474 probe sets were changed by at least two fold in the opposite direction in the dexamethasone plus testosterone group (genes in opposition). Major biological themes represented by genes in opposition included IGF-1 signaling, protein synthesis, myogenesis and muscle development, and ubiquitin conjugases and ligases. Testosterone blocked increased expression of DDIT4 and eIF4EBP1, FOXO1 and of the p85 regulatory subunit of the IGF-1 receptor, while preventing decreased expression of IRS-1. Testosterone blocked decreased expression of LXR and suppressed upregulation of C/EBP beta and delta. Testosterone prevented increase expression of Cdkn1A (p21) and decrease expression of cyclins B and D, as well as many other changes that would be expected to reduce cell cycle progression. Testosterone prevented increased expression of muscle development factors Csrp3 and Mbn1 and blocked reduced expression of Wnt4. These data suggest that testosterone blocks multiple changes in gene expression that, collectively, would otherwise downregulate molecular signals that promote protein synthesis and muscle hypertrophy and that stimulate muscle protein catabolism.
Publication Title
REDD1 is a major target of testosterone action in preventing dexamethasone-induced muscle loss.
Sample Metadata Fields
No sample metadata fields
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