Ezh2 and EZH1 are histone H3 lysine 27 specific methyltransferase. Their hyperactive mutations and overexpression were found in cancer including various hematological malignancies. UNC1999 is a highly selective inhibitor for both enzymes. It suppresses H3K27 tri- and di-methylation globally and inhibits growth of MLL-rearranged acute leukemia cell lines. UNC2400, a di-methylated derivative of UNC1999, is employed an inactive analog compound for assessment of off-target effects. EED knockdown was used to demonstrate gene targets of PRC2.
Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia.
Specimen part, Cell line
View SamplesWe found that a small molecule inhibitor of PRMT4 inhibited cell growth of a subset of multiple myeloma cell lines. To identify biomarkers that predict the sensitivity of myeloma cells to PRMT4 inhibition, we performed transcriptomic analysis of multiple myeloma cell lines. Overall design: Amplicon sequencing of thirteen multiple myeloma cell lines was performed on the Ion Torrent platform. Steady-state gene expression profile of sensitive cells were compaired with that of insensitive cells.
TP-064, a potent and selective small molecule inhibitor of PRMT4 for multiple myeloma.
Specimen part, Cell line, Subject
View SamplesMouse sinoatrial node transcriptome
RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells.
No sample metadata fields
View SamplesThe reprogramming of fibroblast cells to induced pluripotent stem (iPS) cells raises the possibility that a somatic cell could be reprogrammed to an alternative differentiated fate without first becoming a stem/progenitor cell. A large pool of fibroblast cells exists in the post-natal heart, yet no single master regulator of direct cardiac reprogramming has been identified. Here, we report that a combination of three developmental transcription factors (i.e., Gata4, Mef2c and Tbx5) rapidly and efficiently reprogrammed post-natal cardiac or tail-tip fibroblasts directly into differentiated cardiomyocyte-like cells. Induced cardiomyocytes expressed cardiac-specific markers, had a global gene expression profile similar to cardiomyocytes, and contracted spontaneously. Fibroblast cells transplanted into mouse hearts one day after transduction of the three factors also differentiated into cardiomyocyte-like cells. These findings demonstrate that functional cardiomyocytes can be directly reprogrammed from differentiated somatic cells by defined factors. Reprogramming of endogenous or explanted fibroblast cells might provide a source of cardiomyocytes for regenerative approaches.
Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors.
Specimen part
View SamplesCells were reprogrammed from cardiac fibroblasts to cardiomyocytes, in various conditions. These are the iCM cells (induced cardiomyocytes). There are both human and mouse arrays here, as seen below.
In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes.
Specimen part
View Samplesmicroarray was done on Heart tissue from ko and wt
Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2.
No sample metadata fields
View SamplesThe in vitro directed differentiation of pluripotent stem cells (PSCs) through stimulation of developmental signaling pathways can generate mature somatic cell types for basic laboratory studies or regenerative therapies.
Pluripotent stem cell differentiation reveals distinct developmental pathways regulating lung- versus thyroid-lineage specification.
Treatment
View SamplesBACKGROUND: The transcript levels of many genes exhibit significant variation in tissue samples from inbred laboratory mice. A microarray experiment was designed to separate transcript abundance variation across samples from adipose, heart, kidney, and liver tissues of C57BL/6J mice into within-mouse and between-mouse components. Within-mouse variance captures variation due to heterogeneity of gene expression within tissues, RNA-extraction, and array processing. Between-mouse variance reflects differences in transcript levels between these genetically identical mice. Many biological sources can contribute to heterogeneous transcript levels within a tissue sample including inherent stochasticity of biochemical processes such as intrinsic and extrinsic noise within cells and differences in cell-type composition which can result from heterogeneity of stem and progenitor cell populations. Differences in global signaling patterns between individuals and micro-environmental influences such as interactions with pathogens and cage mates can also contribute to variation, but are likely to contribute more to the between-mouse variance component.
Stochastic variation of transcript abundance in C57BL/6J mice.
Sex, Age, Specimen part
View SamplesNkx2.2, Nkx6.1, and Olig2 repressors were overexpressed, singly or in combination, in in vitro-derived mouse neural progenitors to identify thier repression targets Overall design: Overexpression study to identify genes repressed by Nkx2.2, Nkx6.1, and Olig2 in neural progenitors
A direct fate exclusion mechanism by Sonic hedgehog-regulated transcriptional repressors.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Neural-specific Sox2 input and differential Gli-binding affinity provide context and positional information in Shh-directed neural patterning.
Specimen part, Treatment
View Samples