73,618 results match your criteria mouse hematopoietic

Constitutive activation of NF-κB inducing kinase (NIK) in the mesenchymal lineage using Osterix (Sp7)- or Fibroblast-specific protein 1 (S100a4)-Cre drives spontaneous soft tissue sarcoma.

PLoS One 2021 22;16(7):e0254426. Epub 2021 Jul 22.

Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States of America.

Aberrant NF-κB signaling fuels tumor growth in multiple human cancer types including both hematologic and solid malignancies. Chronic elevated alternative NF-κB signaling can be modeled in transgenic mice upon activation of a conditional NF-κB-inducing kinase (NIK) allele lacking the regulatory TRAF3 binding domain (NT3). Here, we report that expression of NT3 in the mesenchymal lineage with Osterix (Osx/Sp7)-Cre or Fibroblast-Specific Protein 1 (FSP1)-Cre caused subcutaneous, soft tissue tumors. Read More

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

Blood 2021 Jul;138(3):221-233

Division of Experimental Hematology and Cancer Biology, Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH.

The Chd8 gene encodes a member of the chromodomain helicase DNA-binding (CHD) family of SNF2H-like adenosine triphosphate (ATP)-dependent chromatin remodeler, the 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. In this study, we identified CHD8 as a specific and essential regulator of normal hematopoiesis. Read More

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The Impact of Sedentary Lifestyle, High-fat Diet, Tobacco Smoke, and Alcohol Intake on the Hematopoietic Stem Cell Niches.

Hemasphere 2021 Aug 19;5(8):e615. Epub 2021 Jul 19.

Department of Hematology, Rigshospitalet, Copenhagen, Denmark.

Hematopoietic stem and progenitor cells maintain hematopoiesis throughout life by generating all major blood cell lineages through the process of self-renewal and differentiation. In adult mammals, hematopoietic stem cells (HSCs) primarily reside in the bone marrow (BM) at special microenvironments called "niches." Niches are thought to extrinsically orchestrate the HSC fate including their quiescence and proliferation. Read More

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Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury.

Front Cell Dev Biol 2021 5;9:637270. Epub 2021 Jul 5.

Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Seri Kembangan, Malaysia.

Extensive clinical efforts have been made to control the severity of dengue diseases; however, the dengue morbidity and mortality have not declined. Dengue virus (DENV) can infect and cause systemic damage in many organs, resulting in organ failure. Here, we present a novel report showing a tailored stem-cell-based therapy that can aid in viral clearance and rescue liver cells from further damage during dengue infection. Read More

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Siglec-6 is a novel target for CAR T-cell therapy in acute myeloid leukemia (AML).

Blood 2021 Jul 21. Epub 2021 Jul 21.

Universitaetsklinikum Wuerzburg, Wuerzburg, Germany.

Acute myeloid leukemia (AML) is attractive for the development of CAR T-cell immunotherapy because AML blasts are susceptible to T-cell-mediated elimination. Here, we introduce sialic-acid-binding immunoglobulin-like lectin (Siglec)-6 as a novel target for CAR T-cells in AML. We designed a Siglec-6-specific CAR with a targeting-domain derived from a human monoclonal antibody JML‑1. Read More

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Cobblestone Area-forming Cell Assay of Mouse Bone Marrow Hematopoietic Stem Cells.

Bio Protoc 2018 May 5;8(9):e2824. Epub 2018 May 5.

Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Bone Marrow Hematopoietic Stem Cells (HSCs) require bone marrow microenvironment for their maintenance and proliferation. Culture of Bone Marrow Mesenchymal Stromal Cells (MSCs) provides appropriate environmental signals for HSCs survival . Here, we provide a detailed protocol that describes culture conditions for MSCs, flow cytometric isolation of HSCs from mouse bone marrow, and perform co-culture of MSCs and HSCs known as Cobblestone area-forming cell (CAFC) assay. Read More

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The P2X4 purinergic receptor has emerged as a potent regulator of hematopoietic stem/progenitor cell mobilization and homing-a novel view of P2X4 and P2X7 receptor interaction in orchestrating stem cell trafficking.

Leukemia 2021 Jul 20. Epub 2021 Jul 20.

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.

Recent evidence indicates that extracellular adenosine triphosphate (eATP), as a major mediator of purinergic signaling, plays an important role in regulating the mobilization and homing of hematopoietic stem progenitor cells (HSPCs). In our previous work we demonstrated that eATP activates the P2X7 ion channel receptor in HSPCs and that its deficiency impairs stem cell trafficking. To learn more about the role of the P2X purinergic receptor family in hematopoiesis, we phenotyped murine and human HSPCs with respect to the seven P2X receptors and observed that, these cells also highly express P2X4 receptors, which shows ~50% sequence similarity to P2X7 subtypes, but that P2X4 cells are more sensitive to eATP and signal much more rapidly. Read More

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B-1 lymphocytes develop independently of Notch signaling during mouse embryonic development.

Development 2021 Jul 20. Epub 2021 Jul 20.

Center for Stem Cell Research and Regenerative Medicine, Institute for Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.

B-1 lymphocytes are a small but unique component of the innate immune-like cells. However, their ontogenic origin is still a matter of debate. While it is widely accepted that B-1 cells originate early in fetal life, whether or not they arise from hematopoietic stem cells (HSCs) is still unclear. Read More

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Distinct skeletal stem cell types orchestrate long bone skeletogenesis.

Elife 2021 Jul 19;10. Epub 2021 Jul 19.

Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States.

Skeletal stem and progenitor cell populations are crucial for bone physiology. Characterization of these cell types remains restricted to heterogenous bulk populations with limited information on whether they are unique or overlap with previously characterized cell types. Here we show, through comprehensive functional and single-cell transcriptomic analyses, that postnatal long bones of mice contain at least two types of bone progenitors with bona fide skeletal stem cell (SSC) characteristics. Read More

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Thymic Egress Is Regulated by T Cell-Derived LTβR Signal and Distinct Thymic Portal Endothelial Cells.

Front Immunol 2021 1;12:707404. Epub 2021 Jul 1.

Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Thymic blood vessels at the perivascular space (PVS) are the critical site for both homing of hematopoietic progenitor cells (HPCs) and egress of mature thymocytes. It has been intriguing how different opposite migrations can happen in the same place. A subset of specialized thymic portal endothelial cells (TPECs) associated with PVS has been identified to function as the entry site for HPCs. Read More

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Pharmacological MEK inhibition promotes polyclonal T-cell reconstitution and suppresses xenogeneic GVHD.

Cell Immunol 2021 Jul 13;367:104410. Epub 2021 Jul 13.

Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.

Rapid immune reconstitution without developing graft-versus-host disease (GVHD) is required for the success of allogeneic hematopoietic stem cell transplantation. Here, we analyzed the effects of pharmacological MEK inhibition on human polyclonal T-cell reconstitution in a humanized mouse GVHD model utilizing deep sequencing-based T-cell receptor (TCR) repertoire analysis. GVHD mice exhibited a skewed TCR repertoire with a common clone within target organs. Read More

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Simultaneous 3-Nitrophenylhydrazine Derivatization Strategy of Carbonyl, Carboxyl and Phosphoryl Submetabolome for LC-MS/MS-Based Targeted Metabolomics with Improved Sensitivity and Coverage.

Anal Chem 2021 Jul 16. Epub 2021 Jul 16.

School of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing 100084, China.

Metabolomics is a powerful and essential technology for profiling metabolic phenotypes and exploring metabolic reprogramming, which enables the identification of biomarkers and provides mechanistic insights into physiology and disease. However, its applications are still limited by the technical challenges particularly in its detection sensitivity for the analysis of biological samples with limited amount, necessitating the development of highly sensitive approaches. Here, we developed a ighly ensitive liquid chromatography tandem mass spectrometry method based on a 3-nitrophenylhydrazine (3-NPH) erivatization strategy that simultaneously targets arbonyl, arboxyl, and hosphoryl groups for argeted etabolomic analysis (HSD-TM) in biological samples. Read More

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Preventive and Therapeutic Effects of a Novel JAK Inhibitor SHR0302 in Acute Graft-Versus-Host Disease.

Cell Transplant 2021 Jan-Dec;30:9636897211033778

Department of Hematology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Acute graft-versus-host disease (aGVHD) is one of the most common complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Janus kinase (JAK) inhibitors are considered as reliable and promising agents for patients with aGVHD. The prophylactic and therapeutic effects of SHR0302, a novel JAK inhibitor, were evaluated in aGVHD mouse models. Read More

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Survival and Functional Immune Reconstitution After Haploidentical Stem Cell Transplantation in -Deficient Mice.

Front Immunol 2021 29;12:693897. Epub 2021 Jun 29.

Division for Allergy, Pneumology and Cystic Fibrosis, Department for Children and Adolescence, Goethe-University, Frankfurt am Main, Germany.

Hematopoietic stem cell transplantation (HSCT) has been proposed as a promising therapeutic opportunity to improve immunity and prevent hematologic malignancies in Ataxia-telangiectasia (A-T). However, experience in the transplantation strategy for A-T patients is still scarce. The aim of this study was to investigate whether different approaches of HSCT are feasible in regard to graft versus host response and sufficient concerning functional immune reconstitution. Read More

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GPX4 and vitamin E cooperatively protect hematopoietic stem and progenitor cells from lipid peroxidation and ferroptosis.

Cell Death Dis 2021 Jul 15;12(7):706. Epub 2021 Jul 15.

Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, China.

Ferroptosis, a newly defined mode of regulated cell death caused by unbalanced lipid redox metabolism, is implicated in various tissue injuries and tumorigenesis. However, the role of ferroptosis in stem cells has not yet been investigated. Glutathione peroxidase 4 (GPX4) is a critical suppressor of lipid peroxidation and ferroptosis. Read More

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Influence of DM-sensitivity on immunogenicity of MHC class II restricted antigens.

J Immunother Cancer 2021 Jul;9(7)

Department of Internal Medicine 5 - Hematology and Internal Oncology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Bayern, Germany

Background: Graft-versus-host-disease (GvHD) is a major problem in allogeneic stem cell transplantation. We previously described two types of endogenous human leukocyte antigen (HLA)-II restricted antigens depending on their behavior towards HLA-DM. While DM-resistant antigens are presented in the presence of HLA-DM, DM-sensitive antigens rely on the expression of HLA-DO-the natural inhibitor of HLA-DM. Read More

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Cardiac Morphology and Collagen Deposition in A Glucose-6-Phosphatase Catalytic Subunit 3 (G6PC3) Knockout Mouse model.

J Med Clin Res Rev 2021 ;5(1)

Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Glucose-6-phosphatase-- β (3), one of multiple isoforms of glucose-6-phosphatase, catalyzes the final step in gluconeogenesis. It is known that mutated G6P3 is associated with severe neutropenia in addition to congenital heart defects, but little is known about the histological changes in cardiac tissue as a result of mutated or deleted G6PC3.

Objectives: We sought to further characterize the histological alterations caused by deleted G6PC3 and determine the role of collagen deposition, myocyte proliferation and apoptosis in these changes. Read More

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January 2021

Enhanced Susceptibility of Galectin-1 Deficient Mice to Experimental Colitis.

Front Immunol 2021 28;12:687443. Epub 2021 Jun 28.

Division of Hematopoietic Innovative Therapies, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER), Madrid, Spain.

Galectin-1 is a -galactoside-binding lectin, ubiquitously expressed in stromal, epithelial, and different subsets of immune cells. Galectin-1 is the prototype member of the galectin family which shares specificity with -galactoside containing proteins and lipids. Immunomodulatory functions have been ascribed to endogenous galectin-1 due to its induction of T cell apoptosis, inhibitory effects of neutrophils and T cell trafficking. Read More

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Inhibition of nicotinamide phosphoribosyltransferase, the rate-limiting enzyme of the nicotinamide adenine dinucleotide salvage pathway, to target glioma heterogeneity through mitochondrial oxidative stress.

Neuro Oncol 2021 Jul 14. Epub 2021 Jul 14.

Division of Neurooncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: Tumor-specific metabolic processes essential for cell survival are promising targets to potentially circumvent intratumoral heterogeneity, a major resistance factor in gliomas. Tumor cells preferentially using nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the salvage pathway for synthesis of NAD, a critical cofactor for diverse biological processes including cellular redox reactions, energy metabolism and biosynthesis. NAMPT is overexpressed in most malignancies, including gliomas, and can serve as a tumor-specific target. Read More

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Short-Term Increased Physical Activity During Early Life Affects High-Fat Diet-Induced Bone Loss in Young Adult Mice.

JBMR Plus 2021 Jul 14;5(7):e10508. Epub 2021 May 14.

Arkansas Children's Nutrition Center Little Rock AR USA.

Mechanical stresses associated with physical activity (PA) have beneficial effects on increasing BMD and improving bone quality. However, a high-fat diet (HFD) and obesity tend to have negative effects on bone, by increasing bone marrow adiposity leading to increased excretion of proinflammatory cytokines, which activate RANKL-induced bone resorption. In the current study, whether short-term increased PA via access to voluntary wheel running during early life has persistent and protective effects on HFD-induced bone resorption was investigated. Read More

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Deficiency of Antioxidative Paraoxonase 2 (Pon2) Leads to Increased Number of Phenotypic LT-HSCs and Disturbed Erythropoiesis.

Oxid Med Cell Longev 2021 25;2021:3917028. Epub 2021 Jun 25.

Department of Pharmacology, Johannes Gutenberg University Medical Center, Mainz, Germany.

Background: Long-term hematopoietic stem cells (LT-HSCs) reside in bone marrow niches with tightly controlled reactive oxygen species (ROS) levels. ROS increase results into LT-HSC differentiation and stem cell exhaustion. Paraoxonase 2 (PON2) has been shown to be important for ROS control. Read More

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A Critical Role of Nuclear m6A Reader YTHDC1 in Leukemogenesis by Regulating MCM Complex-Mediated DNA Replication.

Blood 2021 Jul 13. Epub 2021 Jul 13.

University of Florida, Gainesville, Florida, United States.

YTHDC1 has distinct functions as a nuclear N6-methyladenosine (m6A) reader in regulating RNA metabolism. Here we show that YTHDC1 is overexpressed in Acute Myeloid Leukemia (AML) and that it is required for proliferation and survival of human AML cells. Genetic deletion of Ythdc1 markedly blocks AML development and maintenance as well as self-renewal of leukemia stem cells (LSCs) in vivo in mice. Read More

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Identification of Unique microRNA Expression Patterns in Bone Marrow Hematopoietic Stem and Progenitor Cells after Hemorrhagic Shock and Polytrauma in Young and Old Adult Mice.

J Trauma Acute Care Surg 2021 Jul 9. Epub 2021 Jul 9.

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL.

Background: After severe trauma, the older host experiences more dysfunctional hematopoiesis of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs), and dysfunctional differentiation of circulating myeloid cells into effective innate immune cells. Our main objective was to compare BM HSPC miR responses of old and young mice in a clinically relevant model of severe trauma and shock.

Methods: C57BL/6 adult male mice aged 8-12 weeks (young) and 18-24 months (old) underwent polytrauma and hemorrhagic shock (PT) that engenders the equivalent of major trauma (injury severity score > 15). Read More

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Prebiotic Mannan Oligosaccharide Pretreatment Improves Mice Survival Against Lethal Effects of Gamma Radiation by Protecting GI Tract and Hematopoietic Systems.

Front Oncol 2021 24;11:677781. Epub 2021 Jun 24.

Division of Metabolic Cell Signaling Research, Institute of Nuclear Medicine & Allied Sciences, Delhi, India.

Total body irradiation (TBI) results in critical injuries in a dose dependent manner that primarily damages highly proliferating tissues including hematopoietic stem cells (HSCs) and intestinal crypt stem cells This may result in hematopoietic syndrome leading to bone marrow failure and gastrointestinal syndrome leading to chronic intestinal functional alterations. Death results from the gastrointestinal syndrome due to sepsis, bleeding, dehydration, and multi-system organ failure. We demonstrate that the prebiotic mannan oligosaccharide (MOS) pretreatment substantially prolongs survival in both male and female mice when administered 2 h prior to radiation either through oral or intraperitoneal route. Read More

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Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Vaccine.

Front Immunol 2021 24;12:698737. Epub 2021 Jun 24.

Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States.

Efficacious vaccines are needed to control genital chlamydial diseases in humans and the veterinary industry. We previously reported a (Cab) vaccine comprising recombinant ghosts (rVCG) expressing the conserved and immunogenic N-terminal region of the Cab polymorphic membrane protein D (rVCG-Pmp18.1) protein that protected mice against intravaginal challenge. Read More

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T Cell-Intrinsic CDK6 Is Dispensable for Anti-Viral and Anti-Tumor Responses .

Front Immunol 2021 24;12:650977. Epub 2021 Jun 24.

Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria.

The cyclin-dependent kinase 6 (CDK6) regulates the transition through the G1-phase of the cell cycle, but also acts as a transcriptional regulator. As such CDK6 regulates cell survival or cytokine secretion together with STATs, AP-1 or NF-κB. In the hematopoietic system, CDK6 regulates T cell development and promotes leukemia and lymphoma. Read More

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CD34 protein is expressed in murine, canine, and porcine lungs.

Can J Vet Res 2021 Jul;85(3):161-169

Department of Small Animal Clinical Sciences (Aulakh) and Department of Veterinary Biomedical Sciences (Maltare, Phuong Khanh, Singh), University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B4.

The cell surface protein CD34 is expressed in various human tissues and cells, including hematopoietic stem cells, vascular endothelial cells, mucosal dendritic cells, mast cells, eosinophils, microglia, fibrocytes, muscle satellite cells, and platelets. There is a lack of data on the expression of CD34 in canine and porcine tissues. Therefore, we designed a series of immunoblotting, immunohistochemistry, and immunofluorescence experiments to observe CD34 expression in murine, canine, and porcine lungs. Read More

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Georgian Med News 2021 May(314):139-145

L.I. Medved's Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health of Ukraine (State Enterprise).

Objective - to study the ability of 2,6-dimethylpyridine-N-oxide to modify the cytogenetic effects in mouse bone marrow cells caused by the pro-oxidant mutagen Dioxidine. The cytogenetic activity and mutagen-modifying effect of the plant growth regulator 2,6-dimethylpyridine-N-oxide (Ivin) were studied by the method of accounting for chromosomal aberrations in the bone marrow cells of CD-1 mice (males) with a single joint exposure with Dioxidine. Ivin was administered single orally in the form of an aqueous solution at doses of 710, 71, and 0. Read More

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miRNAs as cell fate determinants of lateral and paraxial mesoderm differentiation from embryonic stem cells.

Dev Biol 2021 Jul 7;478:212-221. Epub 2021 Jul 7.

Department of Medical Genetics, Yeditepe University Medical School, 34755, Istanbul, Turkey. Electronic address:

To date, the role of miRNAs on pluripotency and differentiation of ESCs into specific lineages has been studied extensively. However, the specific role of miRNAs during lateral and paraxial mesoderm cell fate decision is still unclear. To address this, we firstly determined miRNA profile of mouse ESCs differentiating towards lateral and paraxial lineages which were detected using Flk1 and PDGFαR antibodies, and of myogenic and hematopoietic differentiation potential of purified paraxial and lateral mesodermal cells within these populations. Read More

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Mapping the cellular origin and early evolution of leukemia in Down syndrome.

Science 2021 07;373(6551)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.

Children with Down syndrome have a 150-fold increased risk of developing myeloid leukemia, but the mechanism of predisposition is unclear. Because Down syndrome leukemogenesis initiates during fetal development, we characterized the cellular and developmental context of preleukemic initiation and leukemic progression using gene editing in human disomic and trisomic fetal hematopoietic cells and xenotransplantation. GATA binding protein 1 () mutations caused transient preleukemia when introduced into trisomy 21 long-term hematopoietic stem cells, where a subset of chromosome 21 microRNAs affected predisposition to preleukemia. Read More

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