Carbonic anhydrase IX (CA 9) is a transmembrane isoform of carbonic anhydrase (CA) that contributes to an acidification of tumor microenvironment. The expression of CA 9 in cervical tumors was shown to be strongly involved in high incidence of metastasis and poor prognosis.
Carbonic anhydrase IX (CA9) modulates tumor-associated cell migration and invasion.
Specimen part, Disease, Cell line
View SamplesEffect of mycobacterial cell wall component TDM (trehalose dimycolate) of murine macrophage gene expression.
Mycobacterial trehalose dimycolate reprograms macrophage global gene expression and activates matrix metalloproteinases.
Sex, Specimen part, Time
View SamplesB cell CLL/lymphoma 11A (BCL11A) is a transcription factor and regulator of hemoglobin switching that has emerged as a promising therapeutic target for sickle cell disease and thalassemia. In the hematopoietic system, BCL11A is required for B lymphopoiesis, yet its role in other hematopoietic cells, especially hematopoietic stem cells (HSCs) remains elusive. The extensive expression of BCL11A in hematopoiesis implicates context-dependent roles, highlighting the importance of fully characterizing its function as part of ongoing efforts for stem cell therapy and regenerative medicine. Here, we demonstrate that BCL11A is indispensable for normal HSC function. Bcl11a deficiency results in HSC defects, typically observed in the aging hematopoietic system. We find that downregulation of cyclin-dependent kinase 6 (Cdk6), and the ensuing cell-cycle delay, correlate with HSC dysfunction. Our studies define a mechanism for BCL11A in regulation of HSC function and have important implications for the design of therapeutic approaches to targeting BCL11A.
Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype.
Specimen part
View SamplesRad21 is a subunit of cohesin. The main function of cohesin is to hold replicated chromosomes together until cells divide, but it also plays a role in gene expression. To find out which genes might be regulated by cohesin, a study was conducted to look for global changes in gene expression in zebrafish embryos lacking cohesin component Rad21.
Positive regulation of c-Myc by cohesin is direct, and evolutionarily conserved.
Specimen part, Time
View SamplesPlants are sessile organisms and therefore must sense and respond to changes of their surrounding conditions such as ambient temperature, which vary diurnally and seasonally. It is not yet clear how plants sense temperature and integrate this information into their development. We have previously shown that H2A.Z-nucleosomes are evicted in response to warmer temperatures. It is not clear however, whether the link between transcriptional responsiveness and changes in H2A.Z binding in context of temperature shifts is a global trend that can be seen throughout the genome, or the phenomenon is specific to a specialised set of temperature-responsive genes. In addition to the role of H2A.Z-nucleosome dynamics in the transcriptional response to temperature, it was shown that genes strongly misregulated in the h2a.z mutant are enriched for gene categories involved in response to multiple environmental cues. This suggests that H2A.Z could be implicated in the transcriptional response to various environmental inputs, raising the question: What brings the specificity of H2A.Z dynamics in response to temperature? To address this question we have profiled H2A.Z-nucleosome occupancy genome wide (using ChIP-seq) during a time course after temperature variation and compared its dynamics to transcriptional changes. We identified a fast, targeted and transient eviction of H2A.Z associated with transcriptional activation in response to temperature for a few hundreds genes. This eviction is associated with a reduction of the stability of the nucleosome. Moreover the genes with a fast H2A.Z eviction were strongly enriched in heat shock elements in their promoter and we observed a strong association between HSF1 binding and H2AZ eviction at warm temperature. These results highlight the importance of the interplay between transcription factors and chromatin to allow a controlled and dynamics response to temperature. Overall design: RNA-seq were generated in duplicate for seedlings shifted to warm temperature
Transcriptional Regulation of the Ambient Temperature Response by H2A.Z Nucleosomes and HSF1 Transcription Factors in Arabidopsis.
Subject
View SamplesPlants are sessile organisms and therefore must sense and respond to changes of their surrounding conditions such as ambient temperature, which vary diurnally and seasonally. It is not yet clear how plants sense temperature and integrate this information into their development. We have previously shown that H2A.Z-nucleosomes are evicted in response to warmer temperatures. It is not clear however, whether the link between transcriptional responsiveness and changes in H2A.Z binding in context of temperature shifts is a global trend that can be seen throughout the genome, or the phenomenon is specific to a specialised set of temperature-responsive genes. In addition to the role of H2A.Z-nucleosome dynamics in the transcriptional response to temperature, it was shown that genes strongly misregulated in the h2a.z mutant are enriched for gene categories involved in response to multiple environmental cues. This suggests that H2A.Z could be implicated in the transcriptional response to various environmental inputs, raising the question: What brings the specificity of H2A.Z dynamics in response to temperature? To address this question we have profiled H2A.Z-nucleosome occupancy genome wide (using ChIP-seq) during a time course after temperature variation and compared its dynamics to transcriptional changes. We identified a fast, targeted and transient eviction of H2A.Z associated with transcriptional activation in response to temperature for a few hundreds genes. This eviction is associated with a reduction of the stability of the nucleosome. Moreover the genes with a fast H2A.Z eviction were strongly enriched in heat shock elements in their promoter and we observed a strong association between HSF1 binding and H2AZ eviction at warm temperature. These results highlight the importance of the interplay between transcription factors and chromatin to allow a controlled and dynamics response to temperature. Overall design: RNA-seq were generated in duplicate for seedlings shifted to warm temperature
Transcriptional Regulation of the Ambient Temperature Response by H2A.Z Nucleosomes and HSF1 Transcription Factors in Arabidopsis.
Subject
View SamplesGene expression was measured on the Affymetrix platform in primary xenografts, xenograft-derived cell lines, secondary xenografts, normal lung, and primary tumors obtained from chemotherapy naive Small Cell Lung Cancer (SCLC). The SCLC primary xenografts were serially propagated in vivo in immunodeficient mice. Cell lines were derived from each xenograft and grown for 6 months using conventional tissue culture conditions. Secondary xenografts were obtained from cell cultures by re-implantation in immunodeficient mice. Such SCLC laboratory models were analyzed along with conventional SCLC cell lines and the derivative secondary xenografts, with normal lung and primary tumors, to assess irreversible gene expression changes induced by culturing conditions.
A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro.
Disease, Disease stage, Cell line
View SamplesPurpose:To systematically assess the differences between high-throughput single-cell and single-nuclei RNA-seq approaches, we compared Drop-seq and DroNc-seq, two microfluidic-based 3' RNA capture technologies that profile total cellular and nuclear RNA, respectively, during a time course experiment of human induced pluripotent stem cells (iPSCs) differentiating into cardiomyocytes Conclusions: Clustering of time-series transcriptomes from Drop-seq and DroNc-seq revealed six distinct cell types, five of which were found in both techniques. Furthermore, single-cell trajectories reconstructed from both techniques reproduced expected differentiation dynamics. Overall design: Drop-seq and DroNc-seq each on 2 hiPSC cell lines differentiating into cardiomyocytes across 5 time points. DroNc-seq on post-mortem primary heart tissue.
Systematic Comparison of High-throughput Single-Cell and Single-Nucleus Transcriptomes during Cardiomyocyte Differentiation.
Specimen part, Disease, Subject, Time
View SamplesCancer-associated skeletal muscle fatigue is a common problem in clinical oncology that is often associated with cancer cachexia, but is not exclusively observed in cachectic patients. The majority of breast cancer (BC) patients report muscle fatigue despite cachexia being relatively rare in this patient population. The clinically relevant phenotype of muscle fatigue in the absence of frank cachexia has no established model system and no approved therapeutic agents. Here, we utilize a breast cancer patient-derived orthotopic xenograft (BC-PDOX) model to recapitulate the human phenotype of tumor-induced muscle fatigue without muscle wasting, and utilized RNA-sequencing to identify pathways contributing to this clinically common phenomenon.
Human Breast Cancer Xenograft Model Implicates Peroxisome Proliferator-activated Receptor Signaling as Driver of Cancer-induced Muscle Fatigue.
Sex, Specimen part
View SamplesLoss of p120ctn results in dysplasia and invasive cancer in the mouse esophagus and squamous forestomach.
Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene.
Specimen part
View Samples