The Bmi1 Polycomb protein is involved in the epigenetic repressive control of self renewal and survival of cancer initiating cells. In Chronic Myeloid Leukemia (CML), bmi1 expression increases gradually as the disease progresses from a chronic latent phase to a deadly blast crisis. We developped an inducible shRNA system to silence Bmi1 in the human K562 chronic myeloid leukemia (CML) cell line in order to identify new Bmi1-target genes.
The BMI1 polycomb protein represses cyclin G2-induced autophagy to support proliferation in chronic myeloid leukemia cells.
Specimen part, Cell line
View SamplesNo description.
Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis.
Cell line, Subject
View SamplesMicroRNAs inhibit gene expression by recruiting the RNA-induced silencing complex (RISC) to mRNAs in a process termed RNA interference (RNAi). While it is generally accepted that RNAi modulates gene expression pervasively, the number of mRNAs bound and repressed by miRNAs in vivo in individual cell types remains unknown, with estimates ranging from a few hundred genes to many thousands. We examined microRNA activities in primary cells by combining genetic loss of function with RNA-sequencing, quantitative proteomics and High-Throughput Sequencing of RNA isolated by Crosslinking Immunoprecipitation (HITS-CLIP), focusing on miR-144/451, the most highly expressed microRNA locus during red blood cell (RBC) formation. We show that Argonaute (Ago) protein binds over one thousand different mRNAs in a miR-144/451-dependent manner, accounting for one third of all Ago-bound mRNAs. However, only about 100 mRNAs are stabilized in RBC precursors after ablation of the miR-144/451 locus. Thus, Ago-miRNA complexes destabilize only a small subset of bound mRNAs, probably no more than a few hundred in erythroblasts under physiological conditions. Our integrated approach identified more than 50 new miR-144/451 target mRNAs, including Cox10, which facilitates assembly of the mitochondrial cytochrome c oxidase (COX) electron transport complex. Loss of miR-144/451 resulted in increased Cox10 expression, accumulation of the COX complex, and increased mitochondrial membrane potential with no change in mitochondrial mass. Thus, miR-144/451 represses mitochondrial respiration during erythropoiesis by inhibiting Cox10. Overall design: HITS-CLIP analysis of 3 WT mice fetal livers vs 3 miR-144/451 KO mice fetal livers
Regulation of gene expression by miR-144/451 during mouse erythropoiesis.
Cell line, Subject
View Samples5 day RNAi treatment to knockdown Enigma, CG9006, a Drosophila mitochondrial protein with homology to acyl-CoA dehydrogenases.
Enigma, a mitochondrial protein affecting lifespan and oxidative stress response in Drosophila.
No sample metadata fields
View SamplesMuscle stem cells (MuSC) change molecular and functional properties during development. Using a transgenic Tg:Pax7-nGFP mice, we FACS-isolated MuSC from embryonic (E12.5) and foetal (E17.5) stages to understand the differences and similarities amongst the myogenic stem/progenitor populations.
Cell-autonomous Notch activity maintains the temporal specification potential of skeletal muscle stem cells.
Specimen part
View SamplesMouse neural stem cells were generated from conditional knockout mice (Cicflox/flox) or the wild trype control mice (Cic+/+). Cic is conditionally knocked out following expression of Cre-recombinase. Cre-recombinase was incorporated in vitro via adenoviral-Cre transduction.
<i>Cic</i> Loss Promotes Gliomagenesis via Aberrant Neural Stem Cell Proliferation and Differentiation.
Specimen part
View SamplesATC are among the most lethal malignancies, for which there is no effective treatment.
Cell cycle deregulation and TP53 and RAS mutations are major events in poorly differentiated and undifferentiated thyroid carcinomas.
Sex, Specimen part
View SamplesMouse Hammer toe (Hm) shows syndactyly. To reveal the molecular mechanisms of Hm phenotype, we performed microarray analysis to search differencially expressed genes in Hm limb.
Enhancer adoption caused by genomic insertion elicits interdigital <i>Shh</i> expression and syndactyly in mouse.
Specimen part
View SamplesTo define and compare the genome-wide transcriptional signatures of Notch1+ cells in intestinal tumors and in normal ISCs we performed Affymetrix analyses of these two populations.
Lineage tracing of Notch1-expressing cells in intestinal tumours reveals a distinct population of cancer stem cells.
Specimen part
View SamplesA nxnl2 knockout mouse model was created and the transcriptome used to demonstrate that the retina is compromised by the absence of nxnl2.
Nxnl2 splicing results in dual functions in neuronal cell survival and maintenance of cell integrity.
Specimen part
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