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SRP072227
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase, and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. To interrogate the functional requirement for PKM2 during development and tissue homeostasis, we generated germline PKM2 null mice (Pkm2-/-). Unexpectedly, despite being the primary isoform expressed in most wild-type adult tissues, we found that Pkm2-/- mice are viable and fertile. Thus, PKM2 is not required for embryonic or postnatal development. Loss of PKM2 leads to compensatory expression of PKM1 in the tissues that normally express PKM2. Strikingly, PKM2 loss leads to spontaneous development of hepatocellular carcinoma (HCC) with high penetrance that is accompanied by progressive changes in systemic metabolism characterized by altered systemic glucose homeostasis, inflammation, and hepatic steatosis. Therefore, in addition to its role in cancer metabolism, PKM2 plays a role in controlling systemic metabolic homeostasis and inflammation, thereby preventing HCC by a non-cell-autonomous mechanism. Overall design: RNA was isolated from flash frozen ground whole liver tissue of 35 week old PKM2 KO and WT mice. Three independent mice from each condition were used as biological replicates.
Publication Title
Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
3 Cell lines from Apc, p53 (AP) GEMMs were compared to 12 cell lines from Apc, Kras, p53 (AKP) GEMMs.
Publication Title
Development of a colon cancer GEMM-derived orthotopic transplant model for drug discovery and validation.
Sample Metadata Fields
Sex, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We profiled global gene expression for two separate lines of mouse embryonic fibroblasts and find that deletion of PKM2 and expression of PKM1 does not alter global gene expression profiles.
Publication Title
Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 756 Downloadable Samples
- NextSeq 500
Description
Circulating tumor cells (CTCs) play a fundamental role in cancer progression. However, in mice, limited blood volume and the rarity of CTCs in the bloodstream preclude longitudinal, in-depth studies of these cells using existing liquid biopsy techniques. Here, we present an optofluidic system that continuously collects fluorescently-labeled CTCs from a genetically-engineered mouse model for several hours per day over multiple days or weeks. The system is based on a microfluidic cell-sorting chip connected serially to an un-anesthetized mouse via an implanted arteriovenous shunt. Pneumatically-controlled microfluidic valves capture CTCs as they flow through the device and CTC-depleted blood is returned back to the mouse via the shunt. To demonstrate the utility of our system, we profile CTCs isolated longitudinally from animals over a four-day treatment with the BET inhibitor JQ1 using single-cell RNA-Seq (scRNA-Seq) and show that our approach eliminates potential biases driven by inter-mouse heterogeneity that can occur when CTCs are collected across different mice. The CTC isolation and sorting technology presented here provides a research tool to help reveal details of how CTCs change over time, allowing studies to credential changes in CTCs as biomarkers of drug response and facilitating future studies to understand the role of CTCs in metastasis. Overall design: Single-cell RNA-Sequencing of CTCs and primary tumors from a murine model of non-small cell-lung cancer
Publication Title
Optofluidic real-time cell sorter for longitudinal CTC studies in mouse models of cancer.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Proliferating tumor cells use aerobic glycolysis to support their high metabolic demands. Paradoxically, increased glycolysis is often accompanied by expression of the lower activity PKM isoform, effectively constraining lower glycolysis. Here, we report the discovery of novel PKM activators with a unique allosteric binding mode. Characterization of how these compounds impact cancer cells revealed an unanticipated link between glucose and amino acid metabolism. PKM activation resulted in a metabolic rewiring of cancer cells manifested by a profound dependency on the non-essential amino acid serine for continued cell proliferation. Induction of serine auxotrophy by PKM activation was accompanied by reduced carbon flow into the serine biosynthetic pathway and increased expression of high affinity serine transporters. These data support the hypothesis that PKM expression confers metabolic flexibility to cancer cells that allows adaptation to nutrient stress.
Publication Title
Small molecule activation of PKM2 in cancer cells induces serine auxotrophy.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) against MLL-rearranged ALL using xenograft mouse models of MLL-rearranged ALL cell lines and primary patient cells. Panobinostat monotherapy showed strong anti-leukaemic effects, extending survival and reducing overall disease burden. Comprehensive molecular analyses in vitro showed the anti-leukaemic activity in MLL-rearranged ALL to involve depletion of H2B ubiquitination via suppression of the RNF20/RNF40/WAC E3 ligase complex.
Publication Title
The HDAC inhibitor panobinostat (LBH589) exerts in vivo anti-leukaemic activity against MLL-rearranged acute lymphoblastic leukaemia and involves the RNF20/RNF40/WAC-H2B ubiquitination axis.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Comparison of normal neuroblasts with malignant neuroblastomas (low- and high-stage)
Publication Title
Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Comparison between ex vivo immature, mature and stimulated T cells and in vitro generated counterparts. The T cells generated in vitro were cultured on OP9-DL1 stroma supplied with growth factors.
Publication Title
In vitro generation of mature, naive antigen-specific CD8(+) T cells with a single T-cell receptor by agonist selection.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 16 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Genome-wide expression analysis comparison with and without ionizing radiation in p53 mutant and wild type Drosophila larvae
Publication Title
Genome-wide expression analysis identifies a modulator of ionizing radiation-induced p53-independent apoptosis in Drosophila melanogaster.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Study on gene expression in multifunctional protein 2 deficient mice. Liver samples of two days old mice in normal conditions are used. In total 8 arrays were hybridized corresponding to 4 KO mice and 4 WT mice Results: Cholesterol synthesis is induced and ppar alpha targets also differentially expressed between KO and WT.
Publication Title
Coordinate induction of PPAR alpha and SREBP2 in multifunctional protein 2 deficient mice.
Sample Metadata Fields
No sample metadata fields
View Samples