Gene expression profile of acute myeloid leukemia.
Gene expression profile reveals deregulation of genes with relevant functions in the different subclasses of acute myeloid leukemia.
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View Sampleswt1a:GFP labels a population of subepicardial cells in the uninjured ventricle. Here we compare the expression profile of wt1a:GFP-positive cells to the rest of the cells of the ventricle. Overall design: Four paired biological replicates of wt1a:GFP-positive and wt1a:GFP-negative cells obtained from pools of 3-5 zebrafish heart ventricles.
Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart.
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View SamplesContrary to mammals, zebrafish regenerate their heart upon cryoinjury of the cardiac ventricular apex. Regeneration is preceed by a fibrotic response. To understand the contribution of different cell sources to zebrafish cardiac fibrosis we performed an RNASeq including endocardial kdrl:mCherry cells from an uninjured heart, and activated endocardial kdrl:mCherry cells, postnb:citrine fibroblasts and the rest of the cells at 7 days post injury. Overall design: Three to six biological replicates consisting of different cell types obtained from the ventricular apex.
Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart.
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View SamplesContrary to mammals, zebrafish regenerate their heart upon cryoinjury of the ventricular apex. Regeneration is preceeded by a transient fibrotic response. Here we compare the expression profile of fibroblast-like cells at 7 different time points of fibrosis resolution. Using a postnb:CreERT2; ubb:loxP-GFP-loxP-mCherrycz1701 double transgenic line, we permanently label cells that expressed postnb at 3 and 4 days post injury (dpi) with mCherry by administration of 4-OHT. We sequenced mCherry-labelled cells obtained from the ventricular apex at 7 and 60 dpi. Overall design: postnb-derived cells were FAC sorted from a pool of three to five biological samples. Four pools were collected at 7 dpi and three at 60 dpi. RNA was extracted from those pools and further processed for transcriptome analysis.
Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart.
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View SamplesIn vertebrates, the heart has two main layers of cardiac muscle, a peripheral compact layer and an internal trabecular layer. Little is known on the differerences in gene expression between both layers. In zebrafish the outer layer is named cortical layer and the internal also trabecular layer. Here we used a double transgenic line labelling with GFP tbx5-positive cells and cardiomyoctes with nuclear DsRed (nucDsRed) to distinguish cortical from trabecular myocardium. Then, we compared the transcriptome of trabecular and cortical myocardium in the adult zebrafish. We describe that Tbx5a is a good marker of trabecular myocardium. Overall design: Four paired biological replicates consisting on Tbx5-positive and Tbx5-negative adult zebrafish ventricular cardiomyocytes were analysed by RNA-seq to compare their transcriptomic profiles.
Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration.
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View SamplesIxr1 is a transcriptional factor from Saccharomyces cerevisae with high affinity to cisplatin-DNA adducts through their two HMG-box DNA binding domains. Its transcriptional regulation is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Ixr1 function.
Ixr1 Regulates Ribosomal Gene Transcription and Yeast Response to Cisplatin.
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View SamplesThe events regulating human preimplantation development are still largely unknown, due to scarcity of material, ethical and legal limitations, and lack of reliable techniques to faithfully amplify the transcriptome of a single cell. Nonetheless, knowledge in human embryology is gathering renewed interest due to its close relationship with both stem cell biology and epigenetic reprogramming to pluripotency, and their centrality to regenerative medicine. Using carefully timed genome-wide transcript analyses on single oocytes and embryos, the analysis of the data allowed us to uncover a series of successive waves of embryonic transcriptional initiation which start as early as the 2 cell stage. In addition, we identified hierarchical activation of genes involved in the regulation of pluripotency. Finally, we developed HumER, a free database of human preimplantation human development gene expression to serve the scientific community. Importantly, our work links early transcription in the human embryo with the correct execution of the pluripotency program later in development, and paves the way for the identification of factors to improve epigenetic reprogramming.
Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development.
Specimen part, Cell line
View SamplesThe zebrafish heart remarkably regenerates after a severe ventricular damage followed by inflammation, fibrotic tissue deposition and removal concomitant with cardiac muscle replacement. We have investigated the role of the endocardium in this regeneration process. 3D-whole mount imaging in injured hearts revealed that GFP-labelled endocardial cells in ET33mi-60A transgenic fish become rapidly activated and highly proliferative at 3 days post cryoinjury (dpci). Endocardial cells extensively expand within the injury site and organize to form a coherent structure at 9 dpci that persists throughout the regeneration process. Upon injury, endocardial cells strongly up-regulate the Notch pathway ligand delta like4 (dll4) and the Notch receptors notch1b, notch2 and notch3. Expression profiling showed that Notch signalling inhibition affects endocardial gene expression and genes related to extracellular matrix remodelling and inflammation. Gain- and loss-of-function experiments revealed that Notch is required for the organization of the endocardium, attenuation of the inflammatory response and cardiomyocyte proliferation. These results demonstrate a novel structural and signalling role for the endocardium during heart regeneration. Overall design: RNA was extracted from apical tip of heart ventricles 72h after cryoinjured adult zebrafish heart treated with DMSO (Controls) or RO gamma secretase inhibitor at 24 and 48h post injury.
Notch signalling restricts inflammation and <i>serpine1</i> expression in the dynamic endocardium of the regenerating zebrafish heart.
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View SamplesRecent studies suggest that telomerase promotes cell growth by mechanisms that extend beyond the rescue of critically short telomeres. The in vitro model of mTert overexpressing MEFs recapitulates fundamental aspects of the growth-promoting effects of mTert in vivo. First, in Terc-proficient cells, mTert overexpression favors escape from replicative senescence and enhances anchorage-independent growth in response to oncogenic stress, which fits well with previous data showing that mTert overexpression promotes tumor formation. Second, in Terc-deficient cells, retroviral transduction with mTert results in a delayed onset of immortalization and impairs colony formation in response to oncogenic stress, which is in agreement with the inhibitory effect of mTert overexpression on tumorigenesis in a Terc null mouse background. To unravel the molecular targets of telomerase that impact on cell growth, we compared the transcriptome of MEFs, before and after mTert introduction. We found that ectopic expression of mTert was associated with detectable gene expression changes (greater than 1.5-fold; validated by qRT-PCR) of 26 transcripts. Analysis of the observed transcriptional changes indicates that ectopic expression of mTert suppresses in a coordinated manner functionally related genes with overlapping roles in growth arrest, resistance to transformation, and apoptosis. We show that the majority of the telomerase target genes are growth-inhibitory, transforming growth factor-beta (TGF-beta) -inducible genes and provide functional evidence for the potential of telomerase to abrogate TGF-beta -mediated growth inhibition. Thus, in line with the current view that the diversity of TGF-beta responses is not so much a consequence of the use of different signaling pathways but caused by different ways of reading the output from the same basic pathway, we propose that the telomerase status of a cell creates a gene expression pattern that determines how cells read growth inhibitory signals, among them signals propagated through the TGF-beta pathway.
Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-beta signaling.
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View SamplesIn this study we analyzed the behavior of bone marrow MSC (BM-MSC) from MPN patients with the mutation in JAK2V617F. We initially characterized the biological function and gene expression profile changes in BM-MSC from MPN patients when compared to BM-MSC of healthy donors (HD). Then, we established co-cultures between MSC cell lines (HTERT and HS5) and the UKE-1 MPN cell line, and performed RT-PCR to study if the leukemic cells were able to modify the genes related to hematopoietic support.
Mesenchymal stromal cells (MSC) from JAK2+ myeloproliferative neoplasms differ from normal MSC and contribute to the maintenance of neoplastic hematopoiesis.
Specimen part, Disease stage, Subject
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