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GSE57761
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Somatic mitochondrial DNA (mtDNA) mutations contribute to the pathogenesis of age-related disorders, including myelodysplastic syndromes (MDS). The accumulation of mitochondria harboring mtDNA mutations in patients with these disorders suggests a failure of normal mitochondrial quality-control systems. The mtDNA-mutator mice acquire somatic mtDNA mutations via a targeted defect in the proofreading function of the mtDNA polymerase, PolgA, and develop macrocytic anemia similar to that of patients with MDS. We observed an unexpected defect in clearance of dysfunctional mitochondria at specific stages during erythroid maturation in hematopoietic cells from aged mtDNA-mutator mice. Mechanistically, aberrant activation of mechanistic target of rapamycin signaling and phosphorylation of uncoordinated 51-like kinase (ULK) 1 in mtDNA-mutator mice resulted in proteasome mediated degradation of ULK1 and inhibition of autophagy in erythroid cells. To directly evaluate the consequence of inhibiting autophagy on mitochondrial function in erythroid cells harboring mtDNA mutations in vivo, we deleted Atg7 from erythroid progenitors of wildtype and mtDNA-mutator mice. Genetic disruption of autophagy did not cause anemia in wild-type mice but accelerated the decline in mitochondrial respiration and development of macrocytic anemia in mtDNA-mutator mice. These findings highlight a pathological feedback loop that explains how dysfunctional mitochondria can escape autophagy-mediated degradation and propagate in cells predisposed to somatic mtDNA mutations, leading to disease.
Publication Title
Mito-protective autophagy is impaired in erythroid cells of aged mtDNA-mutator mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 34 Downloadable Samples
NextSeq 500
Description
By employing FOXA2-deficient mouse models coupled with LIF repletion, we reveal definitive roles of uterine glands in pregnancy establishment.These studies provide original evidence that uterine glands synchronize embryo-endometrial interactions, coordinate on-time embryo implantation, and impact stromal cell decidualization, thereby ensuring embryo viability, placental growth, and pregnancy success. Overall design: Uterine transcriptomes of control and Foxa2-deficient mice were generated on gestational day (GD) 4 and GD 6 following LIF-repletion. All time points were done in quadruplicates.
Publication Title
Uterine glands coordinate on-time embryo implantation and impact endometrial decidualization for pregnancy success.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The cell differentiation potential of 13-cis retinoic acid (RA) has not succeeded in the clinical treatment of glioblastoma (GBM) so far. However, RA may also induce the expression of disistance genes such as HOXB7 which can be suppressed by Thalidomide (THAL). Therefore, we tested if combined treatment with RA+THAL may inhibit growth of glioblastoma in vivo. Treatment with RA+THAL but not RA or THAL alone significantly inhibited tumour growth. The synergistic effect of RA and THAL was corroborated by the effect on proliferation of glioblastoma cell lines in vitro. HOXB7 was not upregulated but microarray analysis validated by real-time PCR identified four potential resistance genes (IL-8, HILDPA, IGFBPA, and ANGPTL4) whose upregulation by RA was suppressed by THAL. Furthermore, genes coding for small nucleolar RNAs (snoRNA) were identified as a target for RA for the first time, and their upregulation was maintained after combined treatment. Pathway analysis showed upregulation of the Ribosome pathway and downregulation of pathways associated with proliferation and inflammation. Combined treatment with RA + THAL delayed growth of GBM xenografts and suppressed putative resistance genes associated with hypoxia and angiogenesis. This encourages further pre-clinical and clinical studies of this drug combination in GBM.
Publication Title
Inhibition of 13-cis retinoic acid-induced gene expression of reactive-resistance genes by thalidomide in glioblastoma tumours in vivo.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Circulating microvesicles (MVs) have been described as important players in cell-to-cell communication carrying biological information both in normal and pathologic condition. MVs released by cancer cells may incorporate biomolecules such as active lipids, proteins and RNA, which can be delivered and internalized by recipient cells potentially altering gene expression of receiving cells eventually impacting disease progression. In this study, we took advantage of a leukemia in vitro model to investigate MVs as vehicles of protein coding messages. Leukemic cell lines (K562, REH and SHI-1) carrying recurrent translocations were analyzed. In the leukemic cells these translocations are transcribed into oncogenic fusion transcripts. Here, using gene expression microarrays we monitored leukemic fusion transcripts as hallmarks of leukemic cells transcriptome to track mRNA transfer from parental cells to MVs. Transcriptome analysis of K562 cells and released MVs disclosed MVs as not just small scale cells. In fact, a number of transcripts related to membrane activity, cell surface receptors and extracellular communication were enriched in the MVs pool. On the other hand, sets of transcripts related to the basal cellular functions and transcripts of the BCR-ABL oncogenic pathway downstream of the fusion protein were detected in MVs as well as in parental K562 cells. Moreover, through co-culture analyses uptake of leukemic MVs in receiving cells was confirmed and an MV-dosage dependent increase of target cell proliferation was demonstrated.
Publication Title
Expression Profiling of Circulating Microvesicles Reveals Intercellular Transmission of Oncogenic Pathways.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Loss of muscle mass occurs in a variety of diseases including cancer, chronic heart failure, AIDS, diabetes and renal failure, often aggravating pathological progression. Preventing muscle wasting by promoting muscle growth has been proposed as a possible therapeutic approach. Myostatin is an important negative modulator of muscle growth during myogenesis and myostatin inhibitors are attractive drug targets. However, the role of the myostatin pathway in adulthood and the transcription factors involved in the signaling are unclear. Moreover recent results confirm that other TGF members control muscle mass. Using genetic tools we perturbed this pathway in adult myofibers, in vivo, to characterize the downstream targets and their ability to control muscle mass. Smad2 and Smad3 are the transcription factors downstream of myostatin/TGF and induce an atrophy program which is MuRF1 independent and requires FoxO activity. Furthermore Smad2/3 inhibition promotes muscle hypertrophy independent of satellite cells but partially dependent of mTOR signalling. Thus myostatin and Akt pathways cross-talk at different levels. These findings point to myostatin inhibitors as good drugs to promote muscle growth during rehabilitation especially when they are combined with IGF1-Akt activators.
Publication Title
Smad2 and 3 transcription factors control muscle mass in adulthood.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
AIRmax and AIRmin mouse lines show a differential lung inflammatory response and differential lung tumor susceptibility after urethane treatment, thus constituting a good genetic model to investigate differences in gene expression profiles related to inflammatory response and lung tumor susceptibility. The transcript profile of ~24,000 known genes was analyzed in normal lung tissue of untreated and urethane-treated AIRmax and AIRmin mice. In lungs of untreated mice, inflammation associated genes involved in pathways such as leukocyte transendothelial migration, cell adhesion and tight junctions were differentially expressed in AIRmax versus AIRmin mice. Moreover, gene expression levels differed significantly in urethane-treated mice even at 21 days after treatment. In AIRmin mice, modulation of expression of genes involved in pathways associated with inflammatory response paralleled the previously observed persistent infiltration of inflammatory cells in the lung of these mice. In conclusion, a specific gene expression profile in normal lung tissue is associated with mouse line susceptibility or resistance to lung tumorigenesis and with different inflammatory response, and urethane treatment causes a long-lasting alteration of the lung gene expression profile that correlates with persistent inflammatory response of AIRmin mice.
Publication Title
Transcriptome of normal lung distinguishes mouse lines with different susceptibility to inflammation and to lung tumorigenesis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Whole-genome expression studies in peripheral tissues of patients affected by schizophrenia (SCZ) can provide new insights into the molecular basis of the disorder and innovative biomarkers that may be of great usefulness in the clinical practice. Recent evidence suggests that skin fibroblasts could represent a non-neural peripheral model useful to investigate molecular alterations in psychiatric disorders.
Publication Title
Altered gene expression in schizophrenia: findings from transcriptional signatures in fibroblasts and blood.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 37 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Analysis of protein tyrosine phosphatase 1B (PTP1B) deficient mammary glands from nulliparous mice at estrous and pregnancy day 3, 7, 10 and 15. We used a genetically ablated PTP1B mouse model to gain a deeper knowledge of the role PTP1B plays in mammary gland development and to define the mechanism regulated by this phosphatase.
Publication Title
Protein tyrosine phosphatase 1B restrains mammary alveologenesis and secretory differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The aim of this study was to analyze gene response to a 10-week dietary intervention for weight loss in peripheral blood mononuclear cells of overweight/obese male children.
Publication Title
Peripheral blood mononuclear cell gene expression profile in obese boys who followed a moderate energy-restricted diet: differences between high and low responders at baseline and after the intervention.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 17 Downloadable Samples
- Illumina HiSeq 2500
Description
Recent pre-clinical and clinical evidences indicate that hematopoietic stem and progenitor cells (HSPCs) and/or their progeny can serve as vehicles for therapeutic molecule delivery across the blood brain barrier by contributing to the turnover of myeloid cell populations in the brain. However, the differentiation and functional characteristics of the cells reconstituted after transplantation are still to be determined, and in particular whether bona fide microglia could be reconstituted by the donor cell progeny post-transplant to be assessed. We here firstly demonstrate that HSPC transplantation can generate transcriptionally-dependable new microglia through a stepwise process reminiscent of physiological post-natal microglia maturation. Hematopoietic cells able to generate new microglia upon transplantation into myeloablated recipients are retained within human and murine long-term hematopoietic stem cells (HSCs). Similar transcriptionally dependable new microglia cells can also be generated by intra-cerebral ventricular delivery of HSPCs. Importantly, this novel route is associated to a clinically relevant faster and more widespread microglia replacement compared to systemic HSPC injection. Overall, this work supports the relevance and feasibility of employing HSPCs for renewing brain myeloid and microglia cells with new populations endowed with the ability to exert therapeutic effects in the central nervous system, and identifies novel modalities, such as transplantation of enriched stem cell fractions and direct brain delivery of HSPCs, for increasing the actual contribution of the transplanted cells to microgliosis and their therapeutic activity. Overall design: mRNA profiles of µ and TAµ myeloid brain populations were obtained in triplicate mice of Adult control, P10 control and Adult BU-treated mice after GFP Lin-transplantation (both µ and TAµ populations)
Publication Title
Intracerebroventricular delivery of hematopoietic progenitors results in rapid and robust engraftment of microglia-like cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples