PitViper: a software for comparative meta-analysis and annotation of functional screening data.

Recent advancements in shRNA and Cas protein technologies have enabled functional screening methods targeting genes or non-coding regions using single or pooled shRNA and sgRNA. CRISPR-based systems have also been developed for modulating DNA accessibility, resulting in CRISPR-mediated interference (CRISPRi) or activation (CRISPRa) of targeted genes or genomic DNA elements. However, there is still a lack of software tools for integrating diverse array of functional genomics screening outputs that could offer a cohesive framework for comprehensive data integration.

Screening of ETO2-GLIS2-induced Super Enhancers identifies targetable cooperative dependencies in acute megakaryoblastic leukemia.

Super Enhancers (SEs) are clusters of regulatory elements associated with cell identity and disease. However, whether these elements are induced by oncogenes and can regulate gene modules cooperating for cancer cell transformation or maintenance remains elusive. To address this question, we conducted a genome-wide CRISPRi-based screening of SEs in ETO2-GLIS2 acute megakaryoblastic leukemia.

Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease.

Objective: The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages.

Valproic Acid Decreases Endothelial Colony Forming Cells Differentiation and Induces Endothelial-to-Mesenchymal Transition-like Process.

Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor is a widely used anticonvulsant drug. VPA is also under clinical evaluation to be employed in anticancer therapy, as an antithrombotic agent or a molecule to be used in the stem cells expansion protocols. Since endothelial colony forming cells (ECFC) has been identified as the human postnatal vasculogenic cells involved in thrombotic disorders and serve as a promising source of immature cell for vascular repair, objectives of the present study were to determine how VPA contributes to ECFC commitment and their angiogenic properties.

Interleukin-8 release by endothelial colony-forming cells isolated from idiopathic pulmonary fibrosis patients might contribute to their pathogenicity.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms involve a concomitant accumulation of scar tissue together with myofibroblasts activation and a strong abnormal vascular remodeling. Endothelial progenitor cells (ECFC subtype) have been investigated in several human lung diseases as a potential actor in IPF.

Endothelial Microparticles are Associated to Pathogenesis of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms remain unclear but involve a concomitant accumulation of scar tissue together with myofibroblasts activation. Microparticles (MPs) have been investigated in several human lung diseases as possible pathogenic elements, prognosis markers and therapeutic targets.

Egfl7 Represses the Vasculogenic Potential of Human Endothelial Progenitor Cells.

Egfl7 (VE-statin) is a secreted protein mostly specific to the endothelial lineage during development and in the adult and which expression is enhanced during angiogenesis. Egfl7 involvement in human postnatal vasculogenesis remains unresolved yet. Our aim was to assess Egfl7 expression in several angiogenic cell types originating from human bone marrow, peripheral blood, or cord blood.

IGF-1 contributes to the expansion of melanoma-initiating cells through an epithelial-mesenchymal transition process.

Melanoma is a particularly virulent human cancer, due to its resistance to conventional treatments and high frequency of metastasis. Melanomas contain a fraction of cells, the melanoma-initiating cells (MICs), responsible for tumor propagation and relapse. Identification of the molecular pathways supporting MICs is, therefore, vital for the development of targeted treatments.

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In solid organ transplant, immunosuppressive therapy helped to increase graft and patient survival. However, these treatments are associated with toxic risks and infectious or tumor complications. The identification of immunoregulatory properties of regulatory cells and in particular Mesenchymal Stem Cells opens new therapeutic perspectives in the prevention of acute rejection and for the treatment of chronic rejection.

Human bone marrow mesenchymal stem cells regulate biased DNA segregation in response to cell adhesion asymmetry.

Biased DNA segregation is a mitotic event in which the chromatids carrying the original template DNA strands and those carrying the template copies are not segregated randomly into the two daughter cells. Biased segregation has been observed in several cell types, but not in human mesenchymal stem cells (hMSCs), and the factors affecting this bias have yet to be identified. Here, we have investigated cell adhesion geometries as a potential parameter by plating hMSCs from healthy donors on fibronectin-coated micropatterns.

A prospective study of bone marrow hematopoietic and mesenchymal stem cells in type 1 Gaucher disease patients.

Gaucher disease (GD) is an autosomal recessive disorder characterized by lysosomal glucocerebrosidase (GBA) deficiency leading to hematological and skeletal manifestations. Mechanisms underlying these symptoms have not yet been elucidated. In vivo, bone marrow (BM) mesenchymal stem cells (MSCs) have important role in the regulation of bone mass and in the support of hematopoiesis, thus representing potential candidate that could contribute to the disease.

Toll-like receptor 3 regulates cord blood-derived endothelial cell function in vitro and in vivo.

Circulating endothelial progenitor cells (cEPC) are capable of homing to neovascularisation sites, in which they proliferate and differentiate into endothelial cells. Transplantation of cEPC-derived cells, in particular those isolated from umbilical cord blood (UCB), has emerged as a promising approach in the treatment of cardio-vascular diseases. After in vivo transplantation, these cells may be exposed to local or systemic inflammation or pathogens, of which they are a common target.

In vitro development and characterization of a tissue-engineered conduit resembling esophageal wall using human and pig skeletal myoblast, oral epithelial cells, and biologic scaffolds.

Introduction: Tissue engineering represents a promising approach for esophageal replacement, considering the complexity and drawbacks of conventional techniques.

Aim: To create the components necessary to reconstruct in vitro or in vivo an esophageal wall, we analyzed the feasibility and the optimal conditions of human and pig skeletal myoblast (HSM and PSM) and porcine oral epithelial cell (OEC) culture on biologic scaffolds.

Materials And Methods: PSM and HSM were isolated from striated muscle and porcine OECs were extracted from oral mucosa biopsies.

Expression of transforming growth factor β receptor II in mesenchymal stem cells from systemic sclerosis patients.

Objectives: The present work aimed to evaluate the expression of transforming growth factor-β (TGF-β) receptors on bone marrow-derived multipotent mesenchymal stromal cells (MSCs) in patients with systemic sclerosis (SSc) and the consequences of TGF-β activation in these cells, since MSC have potential therapeutic interest for SSc patients and knowing that TGF-β plays a critical role during the development of fibrosis in SSc.

Design: This is a prospective research study using MSC samples obtained from SSc patients and compared with MSC from healthy donors.

Setting: One medical hospital involving collaboration between an internal medicine department for initial patient recruitment, a clinical biotherapeutic unit for MSC preparation and an academic laboratory for research.

Human Muscle Progenitor Cells Displayed Immunosuppressive Effect through Galectin-1 and Semaphorin-3A.

In human skeletal muscle, myoblasts represent the main population of myogenic progenitors. We previously showed that, beside their myogenic differentiation capacities, myoblasts also differentiate towards osteogenic and chondrogenic lineages, some properties generally considered being hallmarks of mesenchymal stem cells (MSCs). MSCs are also characterized by their immunosuppressive potential, through cell-cell contacts and soluble factors, including prostaglandin E-2 (PGE-2), transforming growth factor-β1 (TGF-β1), interleukine-10, or indoleamine 2,3-dioxygenase.

Bone marrow microenvironment in an in vitro model of Gaucher disease: consequences of glucocerebrosidase deficiency.

Gaucher disease (GD) is a lysosomal storage disorder due to glucocerebrosidase (GBA) deficiency. Mechanisms leading to the emergence of hematological and skeletal manifestations observed in GD are poorly explained. Bone marrow (BM) mesenchymal stem cells (MSCs) are multipotent progenitors that participate in the regulation of bone mass.

"To surrender himself, in perfectly liberal inquiry": Walter Pater, many-sidedness, and the conversion novel.

This essay uses Walter Pater's "Marius the Epicurean" (1885) to explore why certain Victorian liberals preferred to see religion as a matter of collective inheritance rather than personal belief. Recent commentators have portrayed the Protestant emphasis on individual conversion as one of the foundations of liberal individualism. Pater's liberalism, however, sees radical breakage with the past as a threat to the humanist ideal of many-sidedness and instead imagines the path of a rich individuality as running precisely through a surrender to the inscriptions of cultural heritage.

Glucocerebrosidase deficiency dramatically impairs human bone marrow haematopoiesis in an in vitro model of Gaucher disease.

One of the cardinal symptoms of type 1 Gaucher Disease (GD) is cytopenia, usually explained by bone marrow (BM) infiltration by Gaucher cells and hypersplenism. However, some cases of cytopenia in splenectomized or treated patients suggest possible other mechanisms. To evaluate intra-cellular glucocerebrosidase (GlcC) activity in immature progenitors and to prove the conduritol B epoxide (CBE)-induced inhibition of the enzyme, we used an adapted flow cytometric technique before assessing the direct effect of GlcC deficiency in functional assays.

In vitro and in vivo analysis of endothelial progenitor cells from cryopreserved umbilical cord blood: are we ready for clinical application?

Umbilical cord blood (CB) represents a main source of circulating endothelial progenitor cells (cEPCs). In view of their clinical use, in either the autologous or allogeneic setting, cEPCs should likely be expanded from CB kept frozen in CB banks. In this study, we compared the expansion, functional features, senescence pattern over culture, and in vivo angiogenic potential of cEPCs isolated from fresh or cryopreserved CB (cryoCB).

Characterization of distinct mesenchymal-like cell populations from human skeletal muscle in situ and in vitro.

Human skeletal muscle is an essential source of various cellular progenitors with potential therapeutic perspectives. We first used extracellular markers to identify in situ the main cell types located in a satellite position or in the endomysium of the skeletal muscle. Immunohistology revealed labeling of cells by markers of mesenchymal (CD13, CD29, CD44, CD47, CD49, CD62, CD73, CD90, CD105, CD146, and CD15 in this study), myogenic (CD56), angiogenic (CD31, CD34, CD106, CD146), hematopoietic (CD10, CD15, CD34) lineages.

A polydioxanone electrospun valved patch to replace the right ventricular outflow tract in a growing lamb model.

A major issue in congenital heart surgery is the lack of viable right ventricular outflow tract (RVOT) replacement materials. Several biomaterials have been used, with different scaffolds and cells, but they have failed to restore a tri-layered RVOT, and reoperations are often required. We investigated the function, histological changes and potential of growth and tissue regeneration of polydioxanone (PDO) electrospun bioabsorbable valved patches seeded with mesenchymal stem cells (MSCs) in the RVOT of growing lambs.

Esophageal replacement by allogenic aorta in a porcine model.

Background: Esophageal replacement is a challenging problem requiring complex reconstruction. In response to the recent success of tracheal replacement by fresh allogenic aorta in humans, we assessed in a pig model the feasibility of circumferential segmental esophageal replacement by a fresh aortic allograft.

Methods: A 4-cm long aortic allograft was interposed after a circumferential 2-cm long resection of the cervical esophagus in 18 minipigs.

Galectin-1 and semaphorin-3A are two soluble factors conferring T-cell immunosuppression to bone marrow mesenchymal stem cell.

In human physiology and animal models, bone marrow mesenchymal stem cells (MSCs) exert an immunosuppressive role in both in vitro and in vivo experiments. However, cellular and molecular mechanisms involved in this process are not clear and remain largely elusive. Several studies have suggested the implication of cell-cell contacts or soluble factors including transforming growth factor-b1 (TGF-b1), interleukin-10 (IL-10), indoleamine 2,3-dioxygenase (IDO), or human leukocyte antigen-G (HLA-G).

Aldehyde dehydrogenase activity identifies a population of human skeletal muscle cells with high myogenic capacities.

Aldehyde dehydrogenase 1A1 (ALDH) activity is one hallmark of human bone marrow (BM), umbilical cord blood (UCB), and peripheral blood (PB) primitive progenitors presenting high reconstitution capacities in vivo. In this study, we have identified ALDH(+) cells within human skeletal muscles, and have analyzed their phenotypical and functional characteristics. Immunohistofluorescence analysis of human muscle tissue sections revealed rare endomysial cells.