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SRP155415
Homo sapiens
6 Downloadable Samples
NextSeq 500
Description
CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor (ER)-positive breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after exposure to palbociclib in ER-positive breast cancer cells. Increased CDK6 in resistant cells was dependent on TGF-ß pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediated transfer of the resistance phenotype between neighboring cell populations. We confirmed these data in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating clinical relevance of this mechanism. Additionally, the CDK4/6 inhibitor resistance phenotype can be reversed in vitro and in vivo by a prolonged drug holiday. Overall design: To analyse the binding targets of miR-432-5p we performed a mRNA pulldown using a synthetic biotin laballed miR-432-5p. RNAseq was performed to identify the captured mRNA.
Publication Title
MicroRNA-Mediated Suppression of the TGF-β Pathway Confers Transmissible and Reversible CDK4/6 Inhibitor Resistance.
Sample Metadata Fields
Specimen part, Subject
View Samples- Gallus gallus
- 9 Downloadable Samples
Affymetrix Chicken Genome Array (chicken)
Description
Excessive accumulation of lipids in the adipose tissue is a major problem in the present-day broiler industry. However, few studies have analyzed the expression of adipose tissue genes that are involved in pathways and mechanisms leading to adiposity in chickens. Gene expression profiling of chicken adipose tissue could provide key information about the ontogenesis of fatness and clarify the molecular mechanisms underlying obesity.
Publication Title
Profiling of chicken adipose tissue gene expression by genome array.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 31 Downloadable Samples
- NextSeq 500
Description
Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL) rearrangements. Herein, we show that co-expression of FLT3-N676K and KMT2A-MLLT3 in human CD34+ cord blood cells primarily cause acute myeloid leukemia (AML) and rarely acute lymphoblastic leukemia (ALL) in immunodeficient mice. By contrast, expression of KMT2A-MLLT3 alone cause ALL, double-positive leukemia (DPL, expressing both CD33 and CD19), or bilineal leukemia (BLL, comprised of distinct myeloid and lymphoid leukemia cells), and rarely AML. Further, AML could only be serially propagated with maintained immunophenotype in secondary recipients when cells co-expressed KMT2A-MLLT3 and FLT3-N676K. Consistent with the idea that activated signaling would allow myeloid cells to engraft and maintain their self-renewal capacity, in a secondary recipient, a de novo KRAS-G13D was identified in myeloid cells previously expressing only KMT2A-MLLT3. Gene expression profiling revealed that KMT2A-MLLT3 DPL had a highly similar gene expression profile to ALL, with both expressing key lymphoid transcription factors and ALL cell surface markers, in line with the DPL cells being ALL cells with aberrant expression of CD33. Taken together, our results highlight the need for constitutive active signaling mutations for driving myeloid leukemia in a human xenograft model of KMT2A-R acute leukemia. Overall design: mRNA sequencing of various immunophenotypic populations from KMT2A-MLLT3 xenograft leukemias with or without FLT3-N676K generated using Illumina NextSeq 500.
Publication Title
FLT3<sup>N676K</sup> drives acute myeloid leukemia in a xenograft model of KMT2A-MLLT3 leukemogenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Immune interferon beta and gamma are essential for mammalian host defence against intracellular pathogens.
Publication Title
GBPs Inhibit Motility of Shigella flexneri but Are Targeted for Degradation by the Bacterial Ubiquitin Ligase IpaH9.8.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- Illumina HiSeq 2000
Description
Cutaneous CD30+ lymphoproliferative disorder (CD30+LPDs), including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma (PCALCL), comprises the second most common group of cutaneous T cell lymphoma. Previously, we reported that special AT-rich sequence-binding protein1 (SATB1), a thymocyte specific chromatin organizer, was over-expressed and promoted malignant T-cell proliferation in a portion of CD30+LPDs, whereas other CD30+LPDs didn't express SATB1 at all. To elucidate the underlying molecular events in CD30+LPDs with differential SATB1 expression, we subjected 4 SATB1+ and 3 SATB1- CD30+LPDs skin biopsies to second-generation RNA-sequencing (RNA-seq). These data provide a significant resource for studies of CD30+LPDs. Overall design: 200ng total RNA samples were extracted and purified from 7 CD30+LPDs skin lesions (4 SATB1+, 3 SATB1-) to establish RNA library. Then the library was qualified through Agilent 2100 bioanalyzer instrument (Agilent Technologies, Santa Clara, CA) and Quantitative real-time polymerase chain reaction. The qualified library was sequenced on an Illumina HiSeqTM 2000 platform using paired-end reads. 10G raw data for each sample were obtained. The reads were aligned to the hg19 genome with SOAPaligner/SOAP2. Gene expression levels were calculated by reads per kilobase transcriptome per million mapped reads(RPKM)method.
Publication Title
SATB1 Defines a Subtype of Cutaneous CD30<sup>+</sup> Lymphoproliferative Disorders Associated with a T-Helper 17 Cytokine Profile.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Haploid pluripotent stem cells, such as haploid embryonic stem cells (haESCs), facilitate the genetic study of recessive traits. In vitro, fish haESCs maintain haploidy in both undifferentiated and differentiated states, but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested. Here, we report that mouse haESCs can differentiate in vitro into haploid epiblast stem cells (haEpiSCs), which maintain an intact haploid genome, unlimited self-renewal potential, and durable pluripotency to differentiate into various tissues in vitro and in vivo. Mechanistically, the maintenance of self-renewal potential depends on the Activin/bFGF pathway. We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells.
Publication Title
Durable pluripotency and haploidy in epiblast stem cells derived from haploid embryonic stem cells in vitro.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with glioma initiating cells (GICs) implicated to be critical for tumor progression and resistance to therapy. KDM1B is involved in regulating GICs'' responses to hypoxia, since over-expression of KDM1B delays the cell growth under hypoxia while knocking-down of KDM1B in GICs promotes their survival and tumorigenic abilities. Overall design: We used RNA-Sequencing to detail the global change of gene expression in GICs with knockdown of KDM1B, and identified de-regulated genes and pathways downstream of KDM1B. CD133+ D456MG GICs were infected with non-targeting control and shRNA of KDM1B. Then RNA was extracted and gene expression was profiled by RNA-Seq.
Publication Title
MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
Severe malnutrition in young children is associated with signs of hepatic dysfunction such as steatosis and hypoalbuminemia, but its etiology is unknown. To investigate the underlying mechanisms of hepatic dysfunction we used a rat model of malnutrition by placing weanling rats on a low protein or control diet (5% or 20% of calories from protein, respectively) for four weeks. Low protein diet-fed rats developed hypoalbuminemia and severe hepatic steatosis, consistent with the human phenotype. Hepatic peroxisome content was decreased and metabolomic analysis indicated impaired peroxisomal function. Loss of peroxisomes was followed by accumulation of dysfunctional mitochondria and decreased hepatic ATP levels. Fenofibrate supplementation restored hepatic peroxisome abundance and increased mitochondrial fatty acid -oxidation capacity, resulting in reduced steatosis and normalization of ATP and plasma albumin levels. These findings provide important insight into the metabolic
Publication Title
Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Vitis vinifera
- 9 Downloadable Samples
- Affymetrix Vitis vinifera (Grape) Genome Array (vitisvinifera)
Description
Solar ultraviolet CUV-Cradiation reaching the Earths surface is little due to the filtering effects of the stratospheric ozone layer. At present, artificial UV-C irradiation is utilized for different biological processes. Grape is a major fruit crop around the world. Research has shown that UV-C irradiation induced the biosynthesis of phenols. However, changes at the molecular level in response to UV-C and leading to these effects are poorly understood. To elucidate the effect of UV-C on expression of genes in grape and the response mechanism, transcript abundance of grape (Vitis vinifera L.) leaves was quantified using the Affymetrix Grape Genome oligonucleotide microarray (15,700 transcripts)
Publication Title
Transcriptomic analysis of grape (Vitis vinifera L.) leaves after exposure to ultraviolet C irradiation.
Sample Metadata Fields
Age, Treatment
View Samples- Homo sapiens
- 189 Downloadable Samples
Description
Estrogen receptor positive (ER+) breast cancers that develop resistance to therapies that target the ER are the most common cause of breast cancer death. Beyond mutations in ER, which occur in 25-30% of patients treated with aromatase inhibitors (AIs), our understanding of clinical mechanisms of resistance to ER-directed therapies remains incomplete. We identified activating HER2 mutations in metastatic biopsies from eight patients with ER+ metastatic breast cancer who had developed resistance to ER-directed agents, including AIs, tamoxifen, and fulvestrant. Examination of treatment-naïve primary tumors in five patients revealed no evidence of pre-existing mutations in four of five patients, suggesting that these mutations were acquired under the selective pressure of ER-directed therapy. These mutations were mutually exclusive with ER mutations, suggesting a distinct mechanism of acquired resistance to ER-directed therapies. In vitro analysis confirmed that these mutations conferred estrogen independence. In addition, and in contrast to ER mutations, these mutations resulted in resistance to tamoxifen, fulvestrant, and the CDK4/6 inhibitor palbociclib. Resistance was overcome by combining ER-directed therapy with the irreversible HER2 kinase inhibitor neratinib, highlighting an effective treatment strategy in these patients. Overall design: Examination of the transcriptional output (mRNA) of the HER2 activating mutations compared with controls under various drugs. Specifically, we expressed the activating mutations S653C, L755S, V777L, and L869R in ER+/HER2- breast cancer cell line (T47D), and controls (GFP, wild-type HER2, kinase-dead HER2, and ESR1 Y537S). Cell were then treated with DMSO, 1µM fulvestrant, 1µM neratinib, 10µM palbociclib, 1µM fulvestrant + 1µM neratinib, or 1µM fulvestrant + 10µM palbociclib for 24 hours. All experimental conditions were done in 6 replicates, sequenced in 3 replicates
Publication Title
Acquired HER2 mutations in ER<sup>+</sup> metastatic breast cancer confer resistance to estrogen receptor-directed therapies.
Sample Metadata Fields
No sample metadata fields
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