Chronic Lymphocytic Leukemia (CLL) cells multiply in secondary lymphoid tissue but the mechanisms leading to their proliferation are still uncertain. In addition to BCR-triggered signals, other microenvironmental factors might well be involved. In proliferation centres, leukemic B cells are in close contact with CD4+CD40L+T cells. Therefore, we here dissected the signals provided by autologous activated T cells (Tact) to CLL cells. Although the gene expression profile induced by Tact was highly similar to that induced by sole CD40 signaling, an obvious difference was that Tact induced proliferation of CLL cells. We determined that stimulation with only CD40L+IL-21 was sufficient to induce robust proliferation in CLL cells. We then defined an IL-21-induced gene signature in CLL, containing components of JAK-STAT and apoptosis pathways, and this signature could be detected in lymph node (LN) samples from patients. Finally, we could detect IL-21 RNA and protein in LN, and IL-21 productionex vivoby LN CD4+CXCR5+ follicular helper T cells. These results indicate that, in addition to BCR signaling, activated T cells might contribute to CLL cell proliferation via CD40 and IL-21. Targeting these signaling pathways might offer new venues for treatment of CLL.
IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells.
Specimen part, Treatment
View SamplesThe NuRD complex is generally thought to repress transcription at both hyper- and hypomethylated regions in the genome. In addition, the complex is involved in the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The ZMYND8 MYND domain directly interacts with PPPL? motifs in the NuRD subunit GATAD2A. Furthermore, GATAD2A and GATAD2B exclusively form homodimers and they thus define mutually exclusive NuRD subcomplexes. ZMYND8 and MBD3 share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and expression of NuRD/ZMYND8 target genes in steady-state asynchronous cells. However, ZMYND8 facilitates immediate recruitment of GATAD2A/NuRD to induced sites of DNA damage. These results thus show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to a distinct NuRD subcomplex. Overall design: RNA-seq samples for HeLa FRT-TO mock, ZMYND8KO, and ZMYND8KO-rescue cells
ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage.
Subject
View SamplesAn early settlement of a complex gut microbiota can protect against gastro-intestinal dysbiosis, but the effects of neonatal microbiota colonization and early life feeding of medium chain triglycerides on the maturation of the porcine gastric mucosa are largely unknown.
The effects of starter microbiota and the early life feeding of medium chain triglycerides on the gastric transcriptome profile of 2- or 3-week-old cesarean delivered piglets.
Specimen part
View SamplesAn early settlement of a complex gut microbiota can protect against gastro-intestinal dysbiosis, but the effects of neonatal microbiota colonization on the maturation of the porcine gastric mucosa are largely unknown.
The effects of starter microbiota and the early life feeding of medium chain triglycerides on the gastric transcriptome profile of 2- or 3-week-old cesarean delivered piglets.
Specimen part
View SamplesArabidopsis plants were treated either with mock or MSB (0.2 mM of Menadione sodium bisulphite). <br></br>Tissue was sampled after 3, 6 and 24 hours.
Molecular analysis of menadione-induced resistance against biotic stress in Arabidopsis.
Age, Specimen part, Compound, Time
View SamplesBone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and a dismal prognosis. To identify and functionally characterize genes involved in the mechanisms of osseous metastasis we developed a murine lung cancer model. Comparative transcriptomic analysis identified genes encoding signaling molecules (such as TCF4 and PRKD3), and cell anchorage related proteins (MCAM, and SUSD5), some of which were basally modulated by TGFbeta in tumor cells and in conditions mimicking tumor-stroma interactions. Triple gene combinations induced not only high osteoclastogenic activity but also a marked enhancement of global metalloproteolytic activities in vitro. These effects were strongly associated with robust bone colonization in vivo, whereas this gene subset was ineffective in promoting local tumor growth and cell homing activity to bone. Interestingly, global inhibition of metalloproteolytic activities and simultaneous TGFbeta blockade in vivo led to increased survival and a remarkable attenuation of bone tumor burden and osteolytic metastasis. Thus, this metastatic gene signature mediates bone-matrix degradation by a dual mechanism of induction of TGFbeta-dependent osteoclastogenic bone resorption and enhancement of stroma-dependent metalloproteolytic activities. Our findings suggest the cooperative contribution of host-derived and cell-autonomous effects directed by a small subset of genes in mediating aggressive osseous colonization.
A novel lung cancer signature mediates metastatic bone colonization by a dual mechanism.
No sample metadata fields
View SamplesGene expression analysis of purified KitL-tomato+ and KitL-tomato- thymic vascular endothelial cells, cortical and medullary thymic epithelial cells from 5 weeks old male kitL-tomato reporter mice Overall design: Differentially expressed genes analysis of thymic stromal cells
A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors.
No sample metadata fields
View SamplesWe isolated QC and xylem cells by sorting GFP+ cells marked with pWOX5::GFP and pTMO5::GFP respectively.
Predicting gene regulatory networks by combining spatial and temporal gene expression data in <i>Arabidopsis</i> root stem cells.
Specimen part
View SamplesWe have investigated the effects of cigarette smoke exposure in three different strains of mice. DBA/2 and C57Bl/6J are susceptible to smoke and develop different lung changes in response to chronic exposure, while ICR mice are resistant to smoke and do not develop emphysema. The present study was carried out to determine early changes in the gene expression profile of mice exposed to cigarette smoke with either a susceptible or resistant phenotype.
Early response of gene clusters is associated with mouse lung resistance or sensitivity to cigarette smoke.
No sample metadata fields
View SamplesSingle cell whole transcriptome analysis of young (2-3 months) and old (20-25 months) mouse HSCs, defined as Lin–Sca-1+c-Kit+150+CD48– . Overall design: Differential gene expression analysis of young and old mouse HSCs (Lin–Sca-1+c-Kit+150+CD48– )
Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells.
No sample metadata fields
View Samples