1,716 results match your criteria hspcs

Macrophage morphological plasticity and migration is Rac signalling and MMP9 dependant.

Sci Rep 2021 May 12;11(1):10123. Epub 2021 May 12.

Emergence of Haematopoietic Stem Cells and Cancer, LPHI, CNRS, INSERM, Univ Montpellier, Montpellier, France.

In vitro, depending on extracellular matrix (ECM) architecture, macrophages migrate either in amoeboid or mesenchymal mode; while the first is a general trait of leukocytes, the latter is associated with tissue remodelling via Matrix Metalloproteinases (MMPs). To assess whether these stereotyped migrations could be also observed in a physiological context, we used the zebrafish embryo and monitored macrophage morphology, behaviour and capacity to mobilise haematopoietic stem/progenitor cells (HSPCs), as a final functional readout. Morphometric analysis identified 4 different cell shapes. Read More

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Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency.

N Engl J Med 2021 May 11. Epub 2021 May 11.

From the Departments of Microbiology, Immunology, and Molecular Genetics (D.B.K., K.L.S., D.A.C.-S., D.T., A.D., A. Icreverzi, P.B., B.C.F., R.P.H., M.C., A.Y., K.M.C., C.E.C., R.Z.), Pediatrics (D.B.K., T.B.M., S.D.O., S.S.), and Pathology and Laboratory Medicine (G.M.C.) and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research (D.B.K., G.M.C.), University of California, Los Angeles (UCLA), and the Department of Pharmaceutical Services, Ronald Reagan UCLA Medical Center (J.T.), Los Angeles, and Stanford School of Medicine, Palo Alto (A.J.S.) - all in California; University College London Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children NHS Foundation Trust (C.B., J.X.-B., V.T., K. Soni, K. Snell, D.L.-R., K.F.B., K.C.G., C.R., N.I., S.A., H.R., C.U., A.J.T., H.B.G.), and Orchard Therapeutics (Europe) (D.A.C.-S., S.A., F.L., M.K., A.S., H.B.G.) - all in London; the National Institute of Allergy and Infectious Diseases (H.L.M.) and the National Human Genome Research Institute (E.G., R.S., F.C.), National Institutes of Health, Bethesda, MD; Cure 4 The Kids Foundation, Las Vegas (A. Ikeda); Cincinnati Children's Hospital Medical Center, Cincinnati (L.R.); Indiana University School of Medicine, Indianapolis (K.C.); Duke University, Durham, NC (R.P., R.H.B., M.H.); Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland (F.C.); and GeneWerk (M.Z., R.H., I.L., M.S.) and the German Cancer Research Center and the National Center for Tumor Diseases (M.Z., M.S.) - all in Heidelberg, Germany.

Background: Severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency (ADA-SCID) is a rare and life-threatening primary immunodeficiency.

Methods: We treated 50 patients with ADA-SCID (30 in the United States and 20 in the United Kingdom) with an investigational gene therapy composed of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a self-inactivating lentiviral vector encoding human . Data from the two U. Read More

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Bone marrow mesenchymal stromal cells in chronic myelomonocytic leukaemia: overactivated WNT/β-catenin signalling by parallel RNA sequencing and dysfunctional phenotypes.

Br J Haematol 2021 May 6. Epub 2021 May 6.

Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080, P.R. China.

Sophisticated cross-talk between bone marrow mesenchymal stromal cells (BM MSCs) and haematopoietic/leukaemic stem cells in patients with myelodysplastic syndromes (MDS) and myeloid leukaemia have been emphasized in previous reports. However, mesenchymal elements in patients with chronic myelomonocytic leukaemia (CMML) were poorly investigated. By utilizing a parallel RNA-sequencing method, we investigated the transcriptional profile and functional defects of primary BM MSCs from patients with CMML for the first time. Read More

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Low Plasma Citrate Levels and Specific Transcriptional Signatures Associated with Quiescence of CD34 Progenitors Predict Azacitidine Therapy Failure in MDS/AML Patients.

Cancers (Basel) 2021 Apr 30;13(9). Epub 2021 Apr 30.

Department of Biology, Faculty of Medicine and Dentistry, Palacky University Olomouc, 775 15 Olomouc, Czech Republic.

To better understand the molecular basis of resistance to azacitidine (AZA) therapy in myelodysplastic syndromes (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), we performed RNA sequencing on pre-treatment CD34 hematopoietic stem/progenitor cells (HSPCs) isolated from 25 MDS/AML-MRC patients of the discovery cohort (10 AZA responders (RD), six stable disease, nine progressive disease (PD) during AZA therapy) and from eight controls. Eleven MDS/AML-MRC samples were also available for analysis of selected metabolites, along with 17 additional samples from an independent validation cohort. Except for two patients, the others did not carry isocitrate dehydrogenase (IDH)1/2 mutations. Read More

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Optimized Intracellular Staining Reveals Heterogeneous Cytokine Production Ability of Murine and Human Hematopoietic Stem and Progenitor Cells.

Front Immunol 2021 14;12:654094. Epub 2021 Apr 14.

MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.

Under stress conditions, hematopoietic stem and progenitor cells (HSPCs) can translate danger signals into a plethora of cytokine signals. These cytokines, or more precisely their combination, instruct HSPCs to modify the magnitude and composition of hematopoietic output in response to the threat, but investigations into the heterogeneous cytokine expression and regulatory mechanisms are hampered by the technical difficulty of measuring cytokine levels in HSPCs at the single-cell level. Here, we optimized a flow cytometry-based method for the simultaneous assessment of multiple intracellular cytokines in HSPCs. Read More

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Integrative transcriptomic analysis of developing hematopoietic stem cells in human and mouse at single-cell resolution.

Biochem Biophys Res Commun 2021 Jun 27;558:161-167. Epub 2021 Apr 27.

Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, Guangdong, 510632, China. Electronic address:

Current understanding of hematopoietic stem cell (HSC) development comes from mouse models is considered to be evolutionarily conserved in human. However, the cross-species comparison of the transcriptomic profiles of developmental HSCs at single-cell level is still lacking. Here, we performed integrative transcriptomic analysis of a series of key cell populations during HSC development in human and mouse, including HSC-primed hemogenic endothelial cells and pre-HSCs in mid-gestational aorta-gonad-mesonephros (AGM) region, and mature HSCs in fetal liver and adult bone marrow. Read More

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Modeling and live imaging of mechanical instabilities in the zebrafish aorta during hematopoiesis.

Sci Rep 2021 Apr 29;11(1):9316. Epub 2021 Apr 29.

Research and Education Center "Materials", Don State Technical University, 1 Gagarin Square, Rostov-on-Don, 344000, Russia.

All blood cells originate from hematopoietic stem/progenitor cells (HSPCs). HSPCs are formed from endothelial cells (ECs) of the dorsal aorta (DA), via endothelial-to-hematopoietic transition (EHT). The zebrafish is a primary model organism to study the process in vivo. Read More

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Connection between Periodontitis-Induced Low-Grade Endotoxemia and Systemic Diseases: Neutrophils as Protagonists and Targets.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91052 Erlangen, Germany.

Periodontitis is considered a promoter of many systemic diseases, but the signaling pathways of this interconnection remain elusive. Recently, it became evident that certain microbial challenges promote a heightened response of myeloid cell populations to subsequent infections either with the same or other pathogens. This phenomenon involves changes in the cell epigenetic and transcription, and is referred to as ''trained immunity''. Read More

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Comparative Transcriptomic Analysis of the Hematopoietic System between Human and Mouse by Single Cell RNA Sequencing.

Cells 2021 Apr 21;10(5). Epub 2021 Apr 21.

Hematology Branch, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA.

(1) Background: mouse models are fundamental to the study of hematopoiesis, but comparisons between mouse and human in single cells have been limited in depth. (2) Methods: we constructed a single-cell resolution transcriptomic atlas of hematopoietic stem and progenitor cells (HSPCs) of human and mouse, from a total of 32,805 single cells. We used Monocle to examine the trajectories of hematopoietic differentiation, and SCENIC to analyze gene networks underlying hematopoiesis. Read More

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The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro.

Molecules 2021 Apr 1;26(7). Epub 2021 Apr 1.

Incubation Center for Advanced Medical Science, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, Japan.

Hematopoietic stem and progenitor cell (HSPC) transplantation is a curative treatment of hematological disorders that has been utilized for several decades. Although umbilical cord blood (UCB) is a promising source of HSPCs, the low dose of HSPCs in these preparations limits their use, prompting need for ex vivo HSPC expansion. To establish a more efficient method to expand UCB HSPCs, we developed the bioactive peptide named SL-13R and cultured UCB HSPCs (CD34+ cells) with SL-13R in animal component-free medium containing a cytokine cocktail. Read More

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Chronic interleukin-1 exposure triggers selection for Cebpa-knockout multipotent hematopoietic progenitors.

J Exp Med 2021 Jun;218(6)

Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO.

The early events that drive myeloid oncogenesis are not well understood. Most studies focus on the cell-intrinsic genetic changes and how they impact cell fate decisions. We consider how chronic exposure to the proinflammatory cytokine, interleukin-1β (IL-1β), impacts Cebpa-knockout hematopoietic stem and progenitor cells (HSPCs) in competitive settings. Read More

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The Nlrp3 inflammasome - the evolving story of its positive and negative effects on hematopoiesis.

Curr Opin Hematol 2021 Apr 23. Epub 2021 Apr 23.

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA Department of Regenerative Medicine, Center for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland.

Purpose Of Review: Hematopoiesis is co-regulated by innate immunity, which is an ancient evolutionary defense mechanism also involved in the development and regeneration of damaged tissues. This review seeks to shed more light on the workings of the Nlrp3 inflammasome, which is an intracellular innate immunity pattern recognition receptor and sensor of changes in the hematopoietic microenvironment, and focus on its role in hematopoieisis.

Recent Findings: Hematopoietic stem progenitor cells (HSPCs) are exposed to several external mediators of innate immunity. Read More

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iPSC modeling of stage-specific leukemogenesis reveals BAALC as a key oncogene in severe congenital neutropenia.

Cell Stem Cell 2021 May 23;28(5):906-922.e6. Epub 2021 Apr 23.

Department of Oncology, Hematology, Immunology, and Rheumatology, University Hospital Tuebingen, 72074 Tuebingen, Germany. Electronic address:

Severe congenital neutropenia (CN) is a pre-leukemic bone marrow failure syndrome that can evolve to acute myeloid leukemia (AML). Mutations in CSF3R and RUNX1 are frequently observed in CN patients, although how they drive the transition from CN to AML (CN/AML) is unclear. Here we establish a model of stepwise leukemogenesis in CN/AML using CRISPR-Cas9 gene editing of CN patient-derived iPSCs. Read More

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Chromatin remodeler CHD8 governs hematopoietic stem/progenitor survival by regulating ATM-mediated P53 protein stability.

Blood 2021 Apr 19. Epub 2021 Apr 19.

Children's Hospital Research Foundation, Cincinnati, Ohio, United States.

The Chd8 gene encodes a member of chromodomain helicase DNA-binding (CHD) family of SNF2H-like ATP-dependent chromatin remodeler, mutations of which define a subtype of Autism spectrum disorders. Increasing evidence from recent studies indicates that ATP-dependent chromatin-remodeling genes are involved in the control of crucial gene-expression programs in hematopoietic stem/progenitor cell (HSPC) regulation. Here we identify CHD8 as a specific and essential regulator of normal hematopoiesis. Read More

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Development of LT-HSC-Reconstituted Non-Irradiated NBSGW Mice for the Study of Human Hematopoiesis .

Front Immunol 2021 25;12:642198. Epub 2021 Mar 25.

Transplantation Research and Immunology Group, John Radcliffe Hospital, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.

Humanized immune system (HIS) mouse models are useful tools for the investigation of human hematopoiesis. However, the majority of HIS models currently in use are biased towards lymphocyte development and fail to support long-term multilineage leucocytes and erythrocytes. Those that achieve successful multilineage reconstitution often require preconditioning steps which are expensive, cause animal morbidity, are technically demanding, and poorly reproducible. Read More

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Innate Immune Memory in Hematopoietic Stem/Progenitor Cells: Myeloid-Biased Differentiation and the Role of Interferon.

Front Immunol 2021 29;12:621333. Epub 2021 Mar 29.

Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.

Innate immune memory was first described for monocytes and other myeloid cells. This memory is designated , in which the host animals that had experienced pathogen infection earlier acquire improved resistance to a second infection. Innate immune memory is mediated by an epigenetic mechanism traced to that is conserved throughout evolution and has been selected for the ability to mount an adaptive response to shifting environments. Read More

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Protocol to produce high-titer retrovirus for transduction of mouse bone marrow cells.

STAR Protoc 2021 Jun 7;2(2):100459. Epub 2021 Apr 7.

School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Regulating gene expression through retroviral infection has been widely used in mouse bone marrow transplantation (BMT) to test the capacity of self-renewal, as well as multi-lineage differentiation of hematopoietic stem and progenitor cells (HSPCs). However, it remains challenging to achieve high transduction efficiency in bone marrow cells as transduction of these cells subsequently leads to transplantation failure. Here, we present a modified protocol to overcome this issue, enabling reproducible and high-efficient retroviral transduction of HSPCs for BMT. Read More

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Hematopoietic stem progenitor cells lacking HLA differ from those lacking GPI-anchored proteins in the hierarchical stage and sensitivity to immune attack in patients with acquired aplastic anemia.

Leukemia 2021 Apr 6. Epub 2021 Apr 6.

Department of Hematology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

To characterize glycosylphosphatidylinositol-anchored protein-deficient (GPI[-]) and HLA-class I allele-lacking (HLA[-]) hematopoietic stem progenitor cells (HSPCs) in acquired aplastic anemia (AA), we studied the peripheral blood (PB) of 56 AA patients in remission who possessed both (n = 13, Group A) or either GPI(-) (n = 34, Group B) and HLA(-) (n = 9, Group C) cell populations. Seventy-seven percent (10/13) of Group A had HLA(-) cells in all lineages of PB cells, including platelets, while only 23% (3/13) had GPI(-) cells in all lineages, and the median percentage of HLA(-) granulocytes in the total granulocytes (21.2%) was significantly higher than that of GPI(-) granulocytes (0. Read More

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Hypoxia-Induced Alpha-Globin Expression in Syncytiotrophoblasts Mimics the Pattern Observed in Preeclamptic Placentas.

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

Department of Clinical Sciences Lund, Division of Obstetrics and Gynecology, Lund University, SE-22184 Lund, Sweden.

Preeclampsia (PE) is a pregnancy disorder associated with placental dysfunction and elevated fetal hemoglobin (HbF). Early in pregnancy the placenta harbors hematopoietic stem and progenitor cells (HSPCs) and is an extramedullary source of erythropoiesis. However, globin expression is not unique to erythroid cells and can be triggered by hypoxia. Read More

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Induction of AML Preleukemic Fusion Genes in HSPCs and DNA Damage Response in Preleukemic Fusion Gene Positive Samples.

Antioxidants (Basel) 2021 Mar 18;10(3). Epub 2021 Mar 18.

Department of Radiobiology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia.

Preleukemic fusion genes (PFGs) occurring after DNA damage in hematopoietic stem progenitor cells (HSPCs) in utero often represent the initial event in the development of childhood leukemia. While the incidence of PFGs characteristic for acute lymphoblastic leukemia (ALL) was relatively well examined by several research groups and estimated to be 1-5% in umbilical cord blood (UCB) of healthy newborns, PFGs that are relevant to acute myeloid leukemia (AML) were poorly investigated. Therefore, this study is focused on the estimation of the incidence of the most frequent AML PFGs in newborns. Read More

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Systemic Administration of G-CSF Accelerates Bone Regeneration and Modulates Mobilization of Progenitor Cells in a Rat Model of Distraction Osteogenesis.

Int J Mol Sci 2021 Mar 28;22(7). Epub 2021 Mar 28.

ISM, CNRS, Aix Marseille University, 13009 Marseille, France.

Granulocyte colony-stimulating factor (G-CSF) was shown to promote bone regeneration and mobilization of vascular and osteogenic progenitor cells. In this study, we investigated the effects of a systemic low dose of G-CSF on both bone consolidation and mobilization of hematopoietic stem/progenitor cells (HSPCs), endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs) in a rat model of distraction osteogenesis (DO). Neovascularization and mineralization were longitudinally monitored using positron emission tomography and planar scintigraphy. Read More

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DOT1L inhibitors block abnormal self-renewal induced by cohesin loss.

Sci Rep 2021 Mar 31;11(1):7288. Epub 2021 Mar 31.

Blood Research Institute, Versiti, 8727 West Watertown Plank Road, Milwaukee, WI, 53226, USA.

Acute myeloid leukemia (AML) is a high-risk malignancy characterized by a diverse spectrum of somatic genetic alterations. The mechanisms by which these mutations contribute to leukemia development and how this informs the use of targeted therapies is critical to improving outcomes for patients. Importantly, how to target loss-of-function mutations has been a critical challenge in precision medicine. Read More

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The Strategies and Challenges of CCR5 Gene Editing in Hematopoietic Stem and Progenitor Cells for the Treatment of HIV.

Stem Cell Rev Rep 2021 Mar 31. Epub 2021 Mar 31.

Centre for Stem Cell Research (A unit of inStem, Bengaluru), Christian Medical College, Vellore, Tamil Nadu, India.

HIV infection continues to be a serious health issue with an alarming global spread, owing to the fact that attempts at developing an effective vaccine or a permanent cure remains futile. So far, the only available treatment for the clinical management of HIV is the combined Anti-Retroviral Therapy (cART), but the long-term cART is associated with metabolic changes, organ damages, and development and transmission of drug resistant HIV strains. Thus, there is a need for the development of one-time curative treatment for HIV infection. Read More

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A single-cell resolution developmental atlas of hematopoietic stem and progenitor cell expansion in zebrafish.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China;

During vertebrate embryogenesis, fetal hematopoietic stem and progenitor cells (HSPCs) exhibit expansion and differentiation properties in a supportive hematopoietic niche. To profile the developmental landscape of fetal HSPCs and their local niche, here, using single-cell RNA-sequencing, we deciphered a dynamic atlas covering 28,777 cells and 9 major cell types (23 clusters) of zebrafish caudal hematopoietic tissue (CHT). We characterized four heterogeneous HSPCs with distinct lineage priming and metabolic gene signatures. Read More

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Activated factor X targeted stored in platelets as an effective gene therapy strategy for both hemophilia A and B.

Clin Transl Med 2021 Mar;11(3):e375

State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, SJTU, Shanghai, China.

Background: Treatment of hemophiliacs with inhibitors remains challenging, and new treatments are in urgent need. Coagulation factor X plays a critical role in the downstream of blood coagulation cascade, which could serve as a bypassing agent for hemophilia therapy. Base on platelet-targeted gene therapy for hemophilia by our and other groups, we hypothesized that activated factor X (FXa) targeted stored in platelets might be effective in treating hemophilia A (HA) and B (HB) with or without inhibitors. Read More

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HOXBLINC long non-coding RNA activation promotes leukemogenesis in NPM1-mutant acute myeloid leukemia.

Nat Commun 2021 03 29;12(1):1956. Epub 2021 Mar 29.

Department of Molecular Medicine, University of Texas Health San Antonio, San Antonio, TX, 78229, USA.

Nucleophosmin (NPM1) is the most commonly mutated gene in acute myeloid leukemia (AML) resulting in aberrant cytoplasmic translocation of the encoded nucleolar protein (NPM1c). NPM1c maintains a unique leukemic gene expression program, characterized by activation of HOXA/B clusters and MEIS1 oncogene to facilitate leukemogenesis. However, the mechanisms by which NPM1c controls such gene expression patterns to promote leukemogenesis remain largely unknown. Read More

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nNOS induction and NOSIP interaction impact granulopoiesis and neutrophil differentiation by modulating nitric oxide generation.

Biochim Biophys Acta Mol Cell Res 2021 Jun 24;1868(7):119018. Epub 2021 Mar 24.

Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, India; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad - Gurgaon Expressway, Faridabad, Haryana 121001, India. Electronic address:

Nitric oxide (NO), a versatile free radical and a signalling molecule, plays an important role in the haematopoiesis, inflammation and infection. Impaired proliferation and differentiation of myeloid cells lead to malignancies and Hematopoietic deficiencies. This study was aimed to define the role of nNOS derived NO in neutrophil differentiation (in-vitro) and granulopoiesis (in-vivo) using multipronged approaches. Read More

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Genetically engineered myeloid cells rebalance the core immune suppression program in metastasis.

Cell 2021 Apr 24;184(8):2033-2052.e21. Epub 2021 Mar 24.

Tumor Microenvironment and Metastasis Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. Electronic address:

Metastasis is the leading cause of cancer-related deaths, and greater knowledge of the metastatic microenvironment is necessary to effectively target this process. Microenvironmental changes occur at distant sites prior to clinically detectable metastatic disease; however, the key niche regulatory signals during metastatic progression remain poorly characterized. Here, we identify a core immune suppression gene signature in pre-metastatic niche formation that is expressed predominantly by myeloid cells. Read More

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