This SuperSeries is composed of the SubSeries listed below.
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
Specimen part
View SamplesLong non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and chromatin modifications, with important functions in development and disease. Here we sought to identify and functionally characterize lncRNAs critical for vascular vertebrate development with significant conservation across species. Genome-wide transcriptomic analyses during human vascular lineage specification enabled the identification of three conserved novel lncRNAs: TERMINATOR, ALIEN and PUNISHER that are specifically expressed in pluripotent stem cells, mesoderm and endothelial cells, respectively. Gene expression profiling, alongside RNA immunoprecipitation coupled to mass spectrometry, revealed a wide range of new molecular networks and protein interactors related to post-transcriptional modifications for all three lncRNAs. Functional experiments in zebrafish and murine embryos, as well as differentiating human cells, confirmed a developmental-stage specific role for each lncRNA during vertebrate development. The identification and functional characterization of these three novel non-coding provide a comprehensive transcriptomic roadmap and shed new light on the molecular mechanisms underlying human vascular development. Overall design: Time course RNA-Seq analysis H1 ESCs differentiated into endothelial cells
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
No sample metadata fields
View SamplesLong non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and chromatin modifications, with important functions in development and disease. Here we sought to identify and functionally characterize lncRNAs critical for vascular vertebrate development with significant conservation across species. Genome-wide transcriptomic analyses during human vascular lineage specification enabled the identification of three conserved novel lncRNAs: TERMINATOR, ALIEN and PUNISHER that are specifically expressed in pluripotent stem cells, mesoderm and endothelial cells, respectively. Gene expression profiling, alongside RNA immunoprecipitation coupled to mass spectrometry, revealed a wide range of new molecular networks and protein interactors related to post-transcriptional modifications for all three lncRNAs. Functional experiments in zebrafish and murine embryos, as well as differentiating human cells, confirmed a developmental-stage specific role for each lncRNA during vertebrate development. The identification and functional characterization of these three novel non-coding provide a comprehensive transcriptomic roadmap and shed new light on the molecular mechanisms underlying human vascular development.
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
Specimen part, Cell line, Treatment
View SamplesIn acute myeloid leukemia (AML), leukemia stem cells (LSCs) play a central role in disease progression and recurrence due to their intrinsic capacity for self-renewal and chemotherapy resistance. Whereas epigenetic regulation balances normal blood stem cell self-renewal and fate decisions, mutation and dysregulation of epigenetic modifiers are now considered fundamental to leukemia initiation and progression. Alterations in miRNA function represent a non-canonical epigenetic mechanism influencing malignant hematopoiesis; however, the function of miRNA in LSC remains undetermined. Here we show that miRNA profiling of fractionated AML populations defines an LSC-specific signature that is highly predictive of patient survival. Gain-of-function genetic analysis demonstrated that miR-126 restrained cell cycle progression, prevented LSC differentiation, and increased LSC self-renewal. miR-126 promoted chemo-resistance, preserving LSC quiescence in part through suppression of the G0-to-G1 gatekeeper, CDK3. Thus, in AML, miRNAs influence patient outcome through post-transcriptional regulation of stemness programs in LSC.
miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
Specimen part, Cell line, Treatment
View SamplesAnalysis of epithelial explants injected with the intracellular domain of Notch (ICD) to block the formation of multi-ciliate cells, either alone or along with FoxJ1. FoxJ1 misexpression leads to the induction fo ectopic cilia in Xenopus laevis epithelia. Results show which genes are affected by FoxJ1 during the induction of ectopic cilia.
The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos.
No sample metadata fields
View SamplesConditional expression of dominant-negative HIF1a in zebrafish cardiomyocytes severely inhibits heart regeneration. To understand more about the mechanism, we performed microarray analysis of wildtype regenerating zebrafish and dnHIF1a regenerating zebrafish to determine which genes are regulated by hypoxia/HIF1a.
Hypoxia induces myocardial regeneration in zebrafish.
Specimen part, Treatment
View SamplesThe BM-derived CD45+/Sca1+ cells are haematopoietic stem/progenitor cells that have the ability to circulate and migrate and engraft to the muscle tissue, and therefore they are of particular interest. Notably, these cells retain their haematopoietic potential, as revealed both by in vitro and in vivo assays; but they also acquire myogenic potential, as shown by their ability to participate in muscle regeneration. Whether, this latter remarkable ability is the result of the reprogramming of the BM-CD45+/Sca1+ cells and the activation of a myogenic molecular program within these cells, remains controversial. This study aims to clarify this aspect of the process, investigating the role of the muscle microenviroment and key myogenic transcription factors.
Bone marrow-derived hematopoietic cells undergo myogenic differentiation following a Pax-7 independent pathway.
No sample metadata fields
View SamplesIschemic cardiopathy is the leading cause of death in the world, for which efficient regenerative therapy is not currently available. In mammals, after a myocardial infarction episode, the damaged myocardium is replaced by scar tissue featuring collagen deposition and tissue remodelling with negligible cardiomyocyte proliferation. Zebrafish, in contrast, display an extensive regenerative capacity as they are able to restore completely lost cardiac tissue after partial ventricular amputation. Due to the lack of genetic lineage tracing evidence, it is not yet clear if new cardiomyocytes arise from existing contractile cells or from an uncharacterised set of progenitors cells. Nonetheless, several genes and molecules have been shown to participate in this process, some of them being cardiomyocyte mitogens in vitro. Though questions as what are the early signals that drive the regenerative response and what is the relative role of each cardiac cell in this process still need to be answered, the zebrafish is emerging as a very valuable tool to understand heart regeneration and devise strategies that may be of potential value to treat human cardiac disease. Here, we performed a genome-wide transcriptome profile analysis focusing on the early time points of zebrafish heart regeneration and compared our results with those of previously published data. Our analyses confirmed the differential expression of several transcripts, and identified additional genes the expression of which is differentially regulated during zebrafish heart regeneration. We validated the microarray data by conventional and/or quantitative RT-PCR. For a subset of these genes, their expression pattern was analyzed by in situ hybridization and shown to be upregulated in the regenerating area of the heart. The specific role of these new transcripts during zebrafish heart regeneration was further investigated ex vivo using primary cultures of zebrafish cardiomyocytes and/or epicardial cells. Our results offer new insights into the biology of heart regeneration in the zebrafish and, together with future experiments in mammals, may be of potential interest for clinical applications.
Transcriptomics approach to investigate zebrafish heart regeneration.
Specimen part, Time
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
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