Megakaryoblastic Leukemia 1 and 2 (MKL1 and 2) are coactivators of the transcription factor Serum Response Factor (SRF). We recently showed that depletion of MKL1 and 2 abolished HCC xenograft growth, associated with oncogene-induced senescence. To identify suitable MKL target genes mediating these effects, we performed microarray analyses using HuH7 hepatocellular carcinoma cells stably expressing shRNA against MKL1/2 (HuH7 MKL1/2 KD). We therefore used a Affymetrix oligonucleotide array and filtered for genes whose expression in HuH7 MKL1/2 KD cells was reduced by a factor of at least 2.5 as compared to control HuH7 cells.
The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma.
Specimen part
View SamplesNeutrophil homeostasis is maintained, in part, by the regulated release of neutrophils from the bone marrow. Constitutive expression of the chemokine CXCL12 by bone marrow stromal cells provides a key retention signal for neutrophils in the bone marrow through activation of its receptor CXCR4. Herein, we show that the ELR chemokines CXCL1 and CXCL2 are constitutively expressed by bone marrow endothelial cells and osteoblasts, and CXCL2 expression is induced in endothelial cells during granulocyte colony-stimulating factor (G-CSF)-induced neutrophil mobilization. Neutrophils lacking CXCR2, the receptor for CXCL1 and CXCL2, are preferentially retained in the bone marrow, reproducing a myelokathexis phenotype. Transient disruption of CXCR4 failed to mobilize CXCR2 neutrophils. However, doubly deficient neutrophils (CXCR2-/- CXCR4-/-) displayed constitutive mobilization, showing that CXCR4 plays a dominant role. Collectively, these data suggest that CXCR2 signaling is a second chemokine axis that interacts antagonistically with CXCR4 to regulate neutrophil release from the bone marrow.
CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow.
Specimen part, Treatment
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 SamplesIn the current study, we have focused on a distinct group of non-coding elements, lncRNA, and profiled renal tissues from three different inbred rat strains. We chose the three strains S, SHR and R for the main purpose of cataloging lncRNA annotations from the most widely used rat models of cardiovascular and renal disease. Overall design: Identification of lncRNAs on the rat genome by next generation RNA sequencing (NGS)
Genome-wide identification of long noncoding RNAs in rat models of cardiovascular and renal disease.
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View SamplesTechnical replicates from BC3 and BCBL1 cell lines were treated with DMSO or 5 micromoles of lenalidomide for 24 hours.
Immunomodulatory drugs target IKZF1-IRF4-MYC axis in primary effusion lymphoma in a cereblon-dependent manner and display synergistic cytotoxicity with BRD4 inhibitors.
Cell line, Treatment
View SamplesWe report here that KSHV viral infection targets the NF-kB pathway which is crucial for cell survival. KSHV protein vFLIP K13 is known to directly interact with cellular protein NEMO of the NF-kB pathway. We used gene expression array to suggets that the interaction of K13 with NEMO is important to activate NF-kB pathway.
NEMO is essential for Kaposi's sarcoma-associated herpesvirus-encoded vFLIP K13-induced gene expression and protection against death receptor-induced cell death, and its N-terminal 251 residues are sufficient for this process.
Specimen part, Cell line
View SamplesIn order to gain insight into the molecular events operating downstream of canonical wnt-signaling in myoblasts, we compared by microarray analysis the transcriptome of myoblast cultured for 4 hours in the presence and absence of Wnt3a.
A Wnt-TGFβ2 axis induces a fibrogenic program in muscle stem cells from dystrophic mice.
Treatment
View SamplesWe report the application of RNA-sequencing for high-throughput profiling of gene expression in hedgehog-responsive stromal cells in normal mouse prostate and mouse prostate tumors. By using the Gli1-GFP knock-in reporter mouse line, we isolated the subset of mouse prostate stromal cells undergoing hedgehog signaling to compare the transcriptomes between PB-MYC prostate tumor and normal prostate in mice at the age of about 45 weeks. Overall design: The mRNA profiles of hedgehog-responsive stromal cells in 45-week old wild type (WT) prostates and PB-MYC prostate tumors were generated by RNA-sequencing, in triplicate, using Illumina HiSeq 2000.
Stromal hedgehog signaling maintains smooth muscle and hampers micro-invasive prostate cancer.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function.
Specimen part
View SamplesIncreased expression of Kruppel like factor 7 (KLF7) is an independent predictor of poor outcome in pediatric acute lymphoblastic leukemia. The contribution of KLF7 to hematopoiesis has not been previously described. Herein, we characterized the effect on murine hematopoiesis of the loss of KLF7 and enforced expression of KLF7. Long-term multilineage engraftment of Klf7-/- cells was comparable to control cells, and self-renewal, as assessed by serial transplantation, was not affected. Enforced expression of KLF7 results in a marked suppression of myeloid progenitor cell growth and a loss of short- and long-term repopulating activity. Interestingly, enforced expression of KLF7, while resulting in multi-lineage growth suppression that extended to hematopoietic stem cells and common lymphoid progenitors, spared T cells and enhanced the survival of early thymocytes. RNA expression profiling of KLF7-overexpressing hematopoietic progenitors identified several potential target genes mediating these effects. Notably, the known KLF7 target Cdkn1a (p21Cip1/Waf1) was not induced by KLF7, and loss of CDKN1A does not rescue the repopulating defect. These results suggest that KLF7 is not required for normal hematopoietic stem and progenitor (HSPC) function, but increased expression, as seen in a subset of lymphoid leukemia, inhibits myeloid cell proliferation and promotes early thymocyte survival.
Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function.
Specimen part
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