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Mus musculus
15 Downloadable Samples
Illumina HiSeq 4000
Description
We describe a critical role for Cdk6 in JAK2V617F+ MPN evolution. The absence of Cdk6 ameliorates clinical symptoms and prolongs survival of JAK2V617F fl/+ vav-Cre mice. The Cdk6 protein interferes with three hallmarks of disease: besides regulating malignant stem cell quiescence, it promotes NFkB signaling and contributes to cytokine production while inhibiting apoptosis. The treatment with palbociclib did not mirror these effects, showing that the functions of Cdk6 in MPN pathogenesis are largely kinase-independent. Overall design: LSK-sorted (FACS) bone marrow cells from 8-week-old VavCre;Jak2+/+; Cdk6+/+, VavCre;Jak2V617F; Cdk6+/+, VavCre;Jak2V617F; Cdk6-/-, VavCre; Jak2+/+; Cdk6-/- mice, and the same cell type from palbociclib-treated (38mg/kg, 3x in one week) VavCre;Jak2V617F; Cdk6+/+ mice, n=3 for all genotypes
Publication Title
CDK6 coordinates <i>JAK2</i> <sup><i>V617F</i></sup> mutant MPN via NF-κB and apoptotic networks.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples
SRP082964- Homo sapiens
- 5 Downloadable Samples
- Illumina HiSeq 2500
Description
Osteosarcoma (OS) is one of the most aggressive bone malignancy. Sub-optimal therapy has irretrievably compromised chances of survival of OS patients for years. Also lack of extensive research on this rare disease has hindered its therapeutic development. Cisplatin (CDDP) is an integral part of current treatment regime for OS. However, despite the proven benefits of CDDP, acquisition of resistance impedes therapy. Also, the molecular effects post CDDP insult in OS cells is poorly understood. Hence, we characterized molecular alterations associated with CDDP-exposure and resistance in OS cells. Resistance to CDDP in OS cells was developed and deep sequencing of mRNA was performed. It depicted an altered transcriptomic signature of resistant cells with enrichment of pathways regulating proliferation. Overall, a significant up-regulation of coding-RNAs and down-regulation of non-coding-RNAs were obtained. Further, analysis of immediate effect of CDDP-shock showed an increase in autophagy and JNK signaling, acting as a pro-survival strategy. Regulatory connections between MAPK signaling and autophagy favoring survival under CDDP-shock was elucidated. Taken together, this is the first study portraying not only global transcriptomic alterations in resistant OS cells but also showing key molecular changes associated with CDDP-insult in OS cells. Our results can be better utilized for future therapeutic benefit. Overall design: We analyzed 5 samples, each being the representative of stages in the acquisition of chemoresistance. Control was the parental HOS cell line with which other comparisons are/will be made in future.
Publication Title
Transcriptomic analysis associated with reversal of cisplatin sensitivity in drug resistant osteosarcoma cells after a drug holiday.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Since the initial discovery that OCT4, SOX2, KLF4 and c-MYC overexpression sufficed for the induction of pluripotency in somatic cells, methodologies replacing the original factors have enhanced our understanding of the reprogramming process. However, unlike in mouse, OCT4 has not been replaced successfully during reprogramming of human cells. Here we report on a strategy to do so. Through a combination of transcriptome and bioinformatic analysis we have identified factors previously characterized as being lineage specifiers that are able to replace OCT4 and SOX2 in the reprogramming of human fibroblasts. Our results show that is possible to replace OCT4 and SOX2 simultaneously with alternative lineage specifiers in the reprogramming of human cells. At a broader level, they also support a model in which counteracting lineage specification networks underlie the induction of pluripotency,
Publication Title
Reprogramming of human fibroblasts to pluripotency with lineage specifiers.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We previously identified multipotent stem cells within the lamina propria of the human olfactory mucosa, located in the nasal cavity. We also demonstrated that this cell type differentiates into neural cells and improves locomotor behavior after transplantation in a rat model of Parkinsons disease. Yet, next to nothing is known about their specific stemness characteristics. We therefore devised a study aiming to compare olfactory lamina propria stem cells from 4 individuals to bone marrow mesenchymal stem cells from 4 age- and gendermatched individuals. Using pangenomic microarrays and immunostaining with 34 cell surface marker antibodies, we show here that olfactory stem cells are closely related to bone marrow stem cells. However, olfactory stem cells exhibit also singular traits. By means of techniques such as proliferation assay, cDNA microarrays, RT-PCR, in vitro and in vivo differentiation, we report that, when compared to bone marrow stem cells, olfactory stem cells display i) a high proliferation rate; ii) a propensity to differentiate into osseous cells and iii) a disinclination to give rise to chondrocytes and adipocytes. Since peripheral olfactory stem cells originate from a neural crest-derived tissue and, as shown here, exhibit an increased expression of neural cellrelated genes, we propose to name them olfactory ecto-mesenchymal stem cells (OE-MSC). Further studies are now required to corroborate the therapeutic potential of OE-MSCs in animal models of bone and brain diseases.
Publication Title
The human nose harbors a niche of olfactory ectomesenchymal stem cells displaying neurogenic and osteogenic properties.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and chromatin modifications, with important functions in development and disease. Here we sought to identify and functionally characterize lncRNAs critical for vascular vertebrate development with significant conservation across species. Genome-wide transcriptomic analyses during human vascular lineage specification enabled the identification of three conserved novel lncRNAs: TERMINATOR, ALIEN and PUNISHER that are specifically expressed in pluripotent stem cells, mesoderm and endothelial cells, respectively. Gene expression profiling, alongside RNA immunoprecipitation coupled to mass spectrometry, revealed a wide range of new molecular networks and protein interactors related to post-transcriptional modifications for all three lncRNAs. Functional experiments in zebrafish and murine embryos, as well as differentiating human cells, confirmed a developmental-stage specific role for each lncRNA during vertebrate development. The identification and functional characterization of these three novel non-coding provide a comprehensive transcriptomic roadmap and shed new light on the molecular mechanisms underlying human vascular development. Overall design: Time course RNA-Seq analysis H1 ESCs differentiated into endothelial cells
Publication Title
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and chromatin modifications, with important functions in development and disease. Here we sought to identify and functionally characterize lncRNAs critical for vascular vertebrate development with significant conservation across species. Genome-wide transcriptomic analyses during human vascular lineage specification enabled the identification of three conserved novel lncRNAs: TERMINATOR, ALIEN and PUNISHER that are specifically expressed in pluripotent stem cells, mesoderm and endothelial cells, respectively. Gene expression profiling, alongside RNA immunoprecipitation coupled to mass spectrometry, revealed a wide range of new molecular networks and protein interactors related to post-transcriptional modifications for all three lncRNAs. Functional experiments in zebrafish and murine embryos, as well as differentiating human cells, confirmed a developmental-stage specific role for each lncRNA during vertebrate development. The identification and functional characterization of these three novel non-coding provide a comprehensive transcriptomic roadmap and shed new light on the molecular mechanisms underlying human vascular development.
Publication Title
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Gene expression from iPSCs before and after gene correction
Publication Title
Targeted gene correction of laminopathy-associated LMNA mutations in patient-specific iPSCs.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 4 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
We determined gene expression profiles which were induced in the chick chorio-allantoic membrane 24 h after application of recombinant human VEGF.
Publication Title
Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Heart failure is a leading cause of mortality and morbidity in the developed world, partly because mammals lack the ability to regenerate heart tissue. Whether this is due to evolutionary loss of regenerative mechanisms present in other organisms or to an inability to activate such mechanisms is currently unclear. Here, we decipher mechanisms underlying heart regeneration in adult zebrafish and show that the molecular regulators of this response are conserved in mammals. We identified miR-99/100 and Let-7a/c, and their protein targets smarca5 and fntb, as critical regulators of cardiomyocyte dedifferentiation and heart regeneration in zebrafish. Although human and murine adult cardiomyocytes fail to elicit an endogenous regenerative response following myocardial infarction, we show that in vivo manipulation of this molecular machinery in mice results in cardiomyocyte dedifferentiation and improved heart functionality after injury. These data provide a proof-of-concept for identifying and activating conserved molecular programs to regenerate the damaged heart. Overall design: RNA-Seq expression profiles of rat cardiomyocytes after knockdown of miR-99/100 and Let-7 miRNAs
Publication Title
In vivo activation of a conserved microRNA program induces mammalian heart regeneration.
Sample Metadata Fields
No sample metadata fields
View Samples