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    162 research outputs found

    Heparin Protects Human Neural Progenitor Cells from Zika Virus-Induced Cell Death While Preserving Their Differentiation into Mature Neuroglial Cells

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    Raw data of the figures reported in the published related article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555206

    Data for "CD32 captures committed haemogenic endothelial cells during human embryonic development"

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    During embryonic development, blood cells emerge from specialized endothelial cells, named hemogenic endothelial cells (HECs). As HECs are rare and transiently found during very early development, it remains difficult to distinguish them from endothelial cells. Here, we performed transcriptomic analysis of 28-32 day human embryos, and observed that the expression of Fc receptor CD32 (FCGR2B), is highly enriched in the endothelial cell population that contains HECs. Functional analyses using human embryonic and hPSC-derived endothelial cells revealed that robust multilineage hematopoietic potential is harbored within CD32+ endothelial cells and showed that 90% of CD32+ endothelial cells are bona fide HECs. Remarkably, these analyses indicated that HECs progress through different states, culminating in FCGR2B expression, at which point cells are irreversibly committed to a hematopoietic fate. These findings provide a precise method for isolating HECs from human embryos and hPSC cultures, thus allowing the efficient generation of hematopoietic cells in vitro

    New orphan disease therapies from the proteome of industrial plasma processing waste- a treatment for aceruloplasminemia

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    Raw data associated to the paper Zanardi, Nardini, et al. Communications Biology (see link). - Proteomics raw data for protein identification associated to Figure 1 of the manuscript are deposited in dedicated repository indicated in the paper (see "link") - Folder " 64CUkCP Biodistribution ": raw data associated to Fig 5 panel (a) and Supplementary Figure 8 describing labelled Cp biodistribution in the brain and blood of mice - Folder "Images choroid plexus": collection of the histochemistry images of choroid plexus stained for iron deposition used to generate data of figure 5 panels (g and h) - Folder "Images Purkinje": collection of the histochemistry images of cerbellum used to count thenumber of Purkinje neurons reported on figure 5 panels (i and j) - Folder "Images liver": collection of the histochemistry images of liver stained with hematoxylin-eosin used to generate figure 7 panels (c and d) - Folder Immunohistochemistry images Cerebellum => Autofluor Purkinje Cells Density: images used to generate data in figure 5 panels (k and l) - Folder Immunohistochemistry images Cerebellum => Astrocyte Density in Arbor Vitae: images used to generate data in figure 6 panels (a and b) - Folder Immunohistochemistry images Cerebellum => GFAP expression in Arbor Vitae: images used to generate data in figure 6 panel (c) - Folder Immunohistochemistry images Cerebellum => Microglia Density in Arbor Vitae: images used to generate data in figure 6 panels (a and d) - Folder Immunohistochemistry images Cerebellum => IBA1 expression in Arbor Vitae: images used to generate data in figure 6 panel (e) - Folder Immunohistochemistry images Hippocampus => Astrocyte Density in CA1 SR: images used to generate data in figure 6 panels (f and g) - Folder Immunohistochemistry images Hippocampus => GFAP expression in CA1 SR: images used to generate data in figure 6 panel (h) - Folder Immunohistochemistry images Hippocampus => Microglia Density in CA1 SR: images used to generate data in figure 6 panels (i and j) - Folder Immunohistochemistry images Hippocampus => IBA1 expression in CA1 SR: images used to generate data in figure 6 panel (k) - Folder Immunohistochemistry images Hippocampus => Neuron Density in CA1 SP: images used to generate data in figure 6 panels (l and m) - Folder Immunohistochemistry images Hippocampus => Thickness of CA1 SP: images used to generate data in figure 6 panel (n) - Folder Immunohistochemistry images Hippocampus => Autofluor Neurons Density in CA1 SP: images used to generate data in figure 6 panel (o) - Folder "WT+CP database ": raw data associated to Supplementary Figure 6 describing the evaluation of toxicity induction in wild-type (WT) mice treated for 4 months with purified ceruloplasmi

    Deep Learning (DL) RF-2016-02364081 dataset for the study titled: ‘Optimizing performance of transformer-based models for fetal brain MR image segmentation’.

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    The dataset includes 172 subjects for a total of 519 fetal rs-fMRI scans with respective brain segmentations. Brain segmentations were obtained with the RS-FetMRI package (https://github.com/NicoloPecco/RS-FetMRI). For each subject the gestational week at scan is reported as the last two digits of the file name. The RF-2016-02364081 DL dataset has been used to train and test deep learning architectures (i.e. Swin-UNETR, UNTER, CNN, GAN) on a fetal brain extraction task for the study titled ‘Optimizing performance of transformer-based models for fetal brain MR image segmentation’. Pretrain weights of Swin-UNETR best model can be found on the ‘weight’ folder (Fetal_pretrain.pth)

    Correction of osteopetrosis in the neonate oc/oc murine model after lentiviral vector gene therapy and nongenotoxic conditioning

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    Introduction: Autosomal recessive osteopetrosis (ARO) is a rare genetic disease, characterized by increased bone density due to defective osteoclast function. Most of the cases are due to TCIRG1 gene mutation, leading to severe bone phenotype and death in the first years of life. The standard therapy is the hematopoietic stem cell transplantation (HSCT), but its success is limited by several constraints. Conversely, gene therapy (GT) could minimize the immune-mediated complications of allogeneic HSCT and offer a prompt treatment to these patients. Methods: The Tcirg1-defective oc/oc mouse model displays a short lifespan and high bone density, closely mirroring the human condition. In this work, we exploited the oc/oc neonate mice to optimize the critical steps for a successful therapy. Results: First, we showed that lentiviral vector GT can revert the osteopetrotic bone phenotype, allowing long-term survival and reducing extramedullary haematopoiesis. Then, we demonstrated that plerixafor-induced mobilization can further increase the high number of HSPCs circulating in peripheral blood, facilitating the collection of adequate numbers of cells for therapeutic purposes. Finally, pre-transplant non-genotoxic conditioning allowed the stable engraftment of HSPCs, albeit at lower level than conventional total body irradiation, and led to long-term survival and correction of bone phenotype, in the absence of acute toxicity. Conclusion: These results will pave the way to the implementation of an effective GT protocol, reducing the transplant-related complication risks in the very young and severely affected ARO patients

    Defining the role of HIF-2alpha in the pathogenesis of acute myeloid leukemia and exploiting its inhibition as a new therapeutic approach to promote leukemia differentiation and exhaustion

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    This dataset represents findings obtained within a project supported by the Italian Ministry of Health (project code: RF-2019-12369841) and focused on investigating the mechanism of myeloid differentiation blockade by the transcription factor HIF-2alpha in acute myeloid leukemia (AML) and the consequences of its inhibition with novel targeted therapies. We found that in AML HIF-2alpha regulates a specific set of target genes involved in transcriptional repression, leading to inhibition of entire gene clusters linked to myeloid difefrentiation. As a consequence, HIF-2alpha blockade via genetic or pharmacologic approaches leads to myeloid differentiation and leukemia debulking. Also, we positioned HIF-2alpha under direct transcriptional control by the prodifferentiation agent all-trans retinoic acid (ATRA) and demonstrated that HIF-2alpha blockade cooperates with ATRA to trigger AML cell differentiation. Links related to this dataset contain: 1. A publication describing part of the results funded by this grant; 2. Source data linked to this publication and deposited in the BioStudies repository (accession number: S-SCDT-10_15252-EMMM_202317810); 3. Sequencing data deposited in the GEO repository

    Heparin Precursors with Reduced Anticoagulant Properties Retain Antiviral and Protective Effects That Potentiate the Efficacy of Sofosbuvir against Zika Virus Infection in Human Neural Progenitor Cells

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    Raw data of the figures reported in the published related article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609960

    Gold nanorod-assisted theranostic solution for non-visible residual disease in bladder cancer

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    The reported raw data are about i) characterization of gold nanorods and ii) hyperthermia experiments carried out in the absence and presence of GNRs as well as well as in the absence and presence of bladder tumor. These data can be used together with those summarized in the supplementary Table S1 and S2 present in the manuscript

    Circulating hematopoietic stem/progenitor cell subsets contribute to human hematopoietic homeostasis

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    In physiological conditions, few circulating hematopoietic stem/progenitor cells (cHSPC) are present in the peripheral blood but their contribution to hematopoietic homeostasis in humans remain unsolved. By integrating advanced immunophenotyping, cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), functional single-cell assays and integration site (IS) clonal tracking, we unveiled the phenotypic composition, the transcriptional features and the biological role of human cHSPC subpopulations in relationship to their bone marrow (BM) counterpart. We found that cHSPC progressively reduced in cell count over aging and are enriched for primitive, lymphoid and erythroid subpopulations, showing pre-activated transcriptional and functional state. Moreover, cHSPC have low expression of multiple BM-retention molecules, but maintain their homing potential after xenotransplantation. By generating a comprehensive Human Organ-Resident HSPC (HuOR) dataset based on scRNAseq data, we detected organ-specific seeding properties of the distinct trafficking HSPC subpopulations. Of note, circulating multi-lymphoid progenitors (MLP) are primed for seeding the thymus and actively contribute to T-cell production at steady state in patients treated with HSPC-gene therapy (GT). Human clonal tracking data from GT patients also showed that cHSPC connect distant BM niches and participate to steady-state hematopoietic production, with primitive cHSPC having the highest re-circulation capability to travel in and out the BM. Finally, in case of hematopoietic impairment, cHSPC composition reflects the BM-HSPC content and might represent a biomarker of the BM state for clinical and research purposes. Overall, our comprehensive work unveiled fundamental insights into the in vivo dynamics of human HSPC trafficking and its role in sustaining hematopoietic homeostasis

    QuantiGene Plex assay

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    Preliminary data for the selection of housekeeping genes suitable for our cells to be used as normaliser for the full experiment that will allow us to identify genes potentially modified by the infection with ZIKV and counteracted with the heparin treatment. Instead of performing RNAseq analyses, we decided to opt for QuantiGene Plex (Thermofisher). This test incorporate branched DNA technology for accurate gene expression profiling. Branched DNA assays allow direct measurement of RNA transcripts using signal amplification (Luminex 200 technology) rather than target amplification. We decided to include 4 conditions: uninfected, uninfected + heparin, ZIKV and ZIKV + heparin, and three time points: 4, 24, 48 h post infection, for a total of 12 samples. We performed three 1:4 serial dilutions of all samples. Then, we load the plate with all undiluted samples + all dilutions made. We performed the experiment according to the manufacturer’s instructions (Thermofisher). Thanks to the Thermofisher free online software, we performed the analyses of the data we obtained from the Luminex reading. From the analyses file, we highlighted the data that were saturated (over 20000 reads), then we remove data from "uninfected + heparin 4h" and "ZIKV 4h" since the preparation was not perfect and the data were not reliable (incorrect serial dilution). We selected the samples in which genes are not saturated (dilution 1:64), and we performed the geometric mean (GEOMEAN) of all genes expressed by the same sample. We divided each values by its GEOMEAN and we calculated the standard deviation (SD). We selected the genes with the lower SD. This experiment allowed us to identify the best 4 housekeeping genes: the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase 1 (PGK1), ubiquitin C (UBC) and the ATPase H+ transporting the A subunit V1 (ATP6V1A)

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