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Hematopoiesis

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https://www.readbyqxmd.com/read/28104796/clonal-hematopoiesis-associated-with-tet2-deficiency-accelerates-atherosclerosis-development-in-mice
#1
José J Fuster, Susan MacLauchlan, María A Zuriaga, Maya N Polackal, Allison C Ostriker, Raja Chakraborty, Chia-Ling Wu, Soichi Sano, Sujatha Muralidharan, Cristina Rius, Jacqueline Vuong, Sophia Jacob, Varsha Muralidhar, Avril A B Robertson, Matthew A Cooper, Vicente Andrés, Karen K Hirschi, Kathleen A Martin, Kenneth Walsh
Human aging is associated with an increased frequency of somatic mutations in hematopoietic cells. Several of these recurrent mutations, including those in the gene encoding the epigenetic modifier enzyme TET2, promote expansion of the mutant blood cells. This "clonal hematopoiesis" correlates with an increased risk of atherosclerotic cardiovascular disease. Here we studied the effects of the expansion of Tet2-mutant cells in atherosclerosis-prone, low-density lipoprotein receptor-deficient (Ldlr-/-) mice. We found that partial bone marrow reconstitution with Tet2-deficient cells was sufficient for their clonal expansion and led to a marked increase in atherosclerotic plaque size...
January 19, 2017: Science
https://www.readbyqxmd.com/read/28102122/advances-in-myeloid-like-cell-origins-and-functions-in-the-model-organism-drosophila-melanogaster
#2
Laure El Chamy, Nicolas Matt, Jean-Marc Reichhart
Drosophila has long served as a valuable model for deciphering many biological processes, including immune responses. Indeed, the genetic tractability of this organism is particularly suited for large-scale analyses. Studies performed during the last 3 decades have proven that the signaling pathways that regulate the innate immune response are conserved between Drosophila and mammals. This review summarizes the recent advances on Drosophila hematopoiesis and immune cellular responses, with a particular emphasis on phagocytosis...
January 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28101170/extramedullary-hematopoiesis-a-report-of-two-cases
#3
Huan-Zhu Zhang, Ying Li, Xin Liu, Bao-Rong Chen, Guo-Hua Yao, Yu-Na Peng
Extramedullary hematopoiesis (EMH) is defined as hematopoiesis occurring in organs outside of the bone marrow. The present report describes two cases of thalassemic patients with paraspinal medullary hematopoiesis and analyzes the clinical manifestations, imaging, pathology, diagnosis and treatment of EMH. In addition, a supplementary review of previously published cases is provided along with a review of the related literature. Computed tomography (CT) of the first case revealed multiple paraspinal masses, and the largest was 6...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100030/epigenetics-in-normal-and-malignant-hematopoiesis-an-overview-and-update-2017
#4
REVIEW
Susumu Goyama, Toshio Kitamura
Epigenetic regulation in hematopoiesis has been a field of rapid expansion. Genome-wide analyses have revealed, and will continue to identify genetic alterations in epigenetic genes that are present in various types of hematopoietic neoplasms. Development of new mouse models for individual epigenetic modifiers has revealed their novel, sometimes unexpected, functions. In this review, we provide an overview of genetic alterations within epigenetic genes in various types of hematopoietic neoplasms. We then summarize the physiologic roles of these epigenetic modifiers during hematopoiesis, and describe therapeutic approaches targeting the epigenetic modifications...
January 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/28099275/characterization-regulation-and-targeting-of-erythroid-progenitors-in-normal-and-disordered-human-erythropoiesis
#5
Brian M Dulmovits, Jimmy Hom, Anupama Narla, Narla Mohandas, Lionel Blanc
PURPOSE OF REVIEW: The erythroid progenitors burst-forming unit-erythroid and colony-forming unit-erythroid have a critical role in erythropoiesis. These cells represent a heterogeneous and poorly characterized population with modifiable self-renewal, proliferation and differentiation capabilities. This review focuses on the current state of erythroid progenitor biology with regard to immunophenotypic identification and regulatory programs. In addition, we will discuss the therapeutic implications of using these erythroid progenitors as pharmacologic targets...
January 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28098348/impact-of-lysosomal-storage-disorders-on-biology-of-mesenchymal-stem-cells-evidences-from-in-vitro-silencing-of-glucocerebrosidase-gba-and-alpha-galactosidase-a-gla-enzymes
#6
T Squillaro, I Antonucci, N Alessio, A Esposito, M Cipollaro, Mab Melone, G Peluso, L Stuppia, U Galderisi
Lysosomal storage disorders (LDS) comprise a group of rare multisystemic diseases resulting from inherited gene mutations that impair lysosomal homeostasis. The most common LSDs, Gaucher disease (GD) and Fabry disease (FD) are caused by deficiencies in the lysosomal glucocerebrosidase (GBA) and alpha-galactosidase A (GLA) enzymes, respectively. Given the systemic nature of enzyme deficiency, we hypothesized that the stem cell compartment of GD and FD patients might be also affected. Among stem cells, mesenchymal stem cells (MSCs) are a commonly investigated population given their role in hematopoiesis and the homeostatic maintenance of many organs and tissues...
January 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28098173/continuous-cell-supply-from-krt7-expressing-hematopoietic-stem-cells-during-native-hematopoiesis-revealed-by-targeted-in-vivo-gene-transfer-method
#7
Yoko Tajima, Keiichi Ito, Ayumi Umino, Adam C Wilkinson, Hiromitsu Nakauchi, Satoshi Yamazaki
The nature of hematopoietic stem cells under normal hematopoiesis remained largely unknown due to the limited assays available to monitor their behavior in situ. Here, we develop a new mouse model to transfer genes specifically into the primitive hematopoietic stem cell compartment through the utilization of a modified Rcas/TVA system. We succeeded in transferring a GFP reporter gene into adult hematopoietic stem cells in vivo, which are predominantly quiescent, by generating pseudotyped-lentivirus. Furthermore, we demonstrate the utility of this system to study neonatal hematopoiesis, a developmental stage that has been difficult to analyze to date...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096534/novel-therapeutic-approach-to-improve-hematopoiesis-in-low-risk-mds-by-targeting-mdscs-with-the-fc-engineered-cd33-antibody-bi-836858
#8
E A Eksioglu, X Chen, K-H Heider, B Rueter, K L McGraw, A A Basiorka, M Wei, A Burnette, P Cheng, J Lancet, R Komrokji, J Djeu, A List, S Wei
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33(+)HLA-DR(-)Lin(-), plays a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28090699/modelling-irf8-deficient-human-hematopoiesis-and-dendritic-cell-development-with-engineered-ips-cells
#9
Stephanie Sontag, Malrun Förster, Jie Qin, Paul Wanek, Saskia Mitzka, Herdit M Schüler, Steffen Koschmieder, Stefan Rose-John, Kristin Seré, Martin Zenke
Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090484/mesenchymal-stromal-cells-in-myeloid-malignancies
#10
REVIEW
Thomas Schroeder, Stefanie Geyh, Ulrich Germing, Rainer Haas
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal myeloid disorders characterized by hematopoietic insufficiency. As MDS and AML are considered to originate from genetic and molecular defects of hematopoietic stem and progenitor cells (HSPC), the main focus of research in this field has focused on the characterization of these cells. Recently, the contribution of BM microenvironment to the pathogenesis of myeloid malignancies, in particular MDS and AML has gained more interest. This is based on a better understanding of its physiological role in the regulation of hematopoiesis...
December 2016: Blood Research
https://www.readbyqxmd.com/read/28088988/clonal-hematopoiesis
#11
REVIEW
Max Jan, Benjamin L Ebert, Siddhartha Jaiswal
Cancer results from multistep pathogenesis, yet the pre-malignant states that precede the development of many hematologic malignancies have been difficult to identify. Recent genomic studies of blood DNA from tens of thousands of people have revealed the presence of remarkably common, age-associated somatic mutations in genes associated with hematologic malignancies. These somatic mutations drive the expansion from a single founding cell to a detectable hematopoietic clone. Owing to the admixed nature of blood that provides a sampling of blood cell production throughout the body, clonal hematopoiesis is a rare view into the biology of pre-malignancy and the direct effects of pre-cancerous lesions on organ dysfunction...
January 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28088987/molecular-mechanisms-underlying-lineage-bias-in-aging-hematopoiesis
#12
REVIEW
Harold K Elias, David Bryder, Christopher Y Park
Although hematopoietic stem cells (HSCs) have traditionally been thought to possess the ability to give rise to all the mature cell types in the hematopoietic system, this conception of hematopoiesis was based on evaluation of hematopoietic output from large numbers of HSCs using transplantation models.  More recent studies evaluating HSCs at the clonal or near-clonal level, both in transplantation studies and during in situ hematopoiesis, have established that individual HSCs can exhibit lineage bias, giving rise to myeloid-biased, lymphoid-biased, or more balanced differentiation, with the proportion of myeloid-biased HSCs increasing with age...
January 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28088986/age-associated-changes-in-human-hematopoietic-stem-cells
#13
REVIEW
Wendy W Pang, Stanley L Schrier, Irving L Weissman
Aging has a broad impact on the function of the human hematopoietic system. This review will focus primarily on the effect of aging on the human hematopoietic stem cell (HSC) population. With age, even though human HSCs increase in number, they have decreased self-renewal capacity and reconstitution potential upon transplantation. As a population, human HSCs become more myeloid-biased in their differentiation potential. This is likely due to the human HSC population becoming more clonal with age, selecting for myeloid-biased HSC clones...
January 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28088981/hematopoiesis-in-aging-current-concepts-and-challenges
#14
EDITORIAL
Christopher Y Park
No abstract text is available yet for this article.
January 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28087539/quantitative-stability-of-hematopoietic-stem-and-progenitor-cell-clonal-output-in-transplanted-rhesus-macaques
#15
Samson J Koelle, Diego A Espinoza, Chuanfeng Wu, Jason Xu, Rong Lu, Brian Li, Robert E Donahue, Cynthia E Dunbar
Autologous transplantation of hematopoietic stem and progenitor cells lentivirally labeled with unique oligonucleotide barcodes flanked by sequencing primer targets enables quantitative assessment of the self-renewal and differentiation patterns of these cells in a myeloablative rhesus macaque model. Compared with other approaches to clonal tracking, this approach is highly quantitative and reproducible. We documented very stable multipotent long-term hematopoietic clonal output of monocytes, granulocytes, B cells and T cells from a polyclonal pool of hematopoietic stem and progenitor cells in four macaques followed for up to 49 months post-transplantation...
January 13, 2017: Blood
https://www.readbyqxmd.com/read/28087428/polycomb-complexes-prc1-and-their-function-in-hematopoiesis
#16
REVIEW
Miguel Vidal, Katharzina Starowicz
Hematopoiesis, the process by which blood cells are continuously produced, is one of the best studied differentiation pathways. Hematological diseases are associated to reiterated mutations in genes encoding important gene expression regulators, including chromatin regulators. Among them, the Polycomb group (PcG) of proteins is an essential system of gene silencing involved in the maintenance of cell identities during differentiation. PcG proteins assemble into two major types of Polycomb repressive complexes (PRC) endowed with distinct histone tail modifying activities...
January 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28081565/leucine-rich-%C3%AE-2-glycoprotein-a-novel-neutrophil-granule-protein-and-modulator-of-myelopoiesis
#17
Lawrence J Druhan, Amanda Lance, Shimena Li, Andrea E Price, Jacob T Emerson, Sarah A Baxter, Jonathan M Gerber, Belinda R Avalos
Leucine-rich α2 glycoprotein (LRG1), a serum protein produced by hepatocytes, has been implicated in angiogenesis and tumor promotion. Our laboratory previously reported the expression of LRG1 in murine myeloid cell lines undergoing neutrophilic granulocyte differentiation. However, the presence of LRG1 in primary human neutrophils and a role for LRG1 in regulation of hematopoiesis have not been previously described. Here we show that LRG1 is packaged into the granule compartment of human neutrophils and secreted upon neutrophil activation to modulate the microenvironment...
2017: PloS One
https://www.readbyqxmd.com/read/28081132/the-janus-faced-nature-of-mir-22-in-hematopoiesis-is-it-an-oncogenic-tumor-suppressor-or-rather-a-tumor-suppressive-oncogene
#18
Alexander Arthur Wurm, Daniel G Tenen, Gerhard Behre
No abstract text is available yet for this article.
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28079523/symbiont-induced-odorant-binding-proteins-mediate-insect-host-hematopoiesis
#19
Joshua B Benoit, Aurélien Vigneron, Nichole A Broderick, Yineng Wu, Jennifer S Sun, John R Carlson, Serap Aksoy, Brian L Weiss
Symbiotic bacteria assist in maintaining homeostasis of the animal immune system. However, the molecular mechanisms that underlie symbiont-mediated host immunity are largely unknown. Tsetse flies (Glossina spp.) house maternally transmitted symbionts that regulate the development and function of their host's immune system. Herein we demonstrate that the obligate mutualist, Wigglesworthia, up-regulates expression of odorant binding protein six in the gut of intrauterine tsetse larvae. This process is necessary and sufficient to induce systemic expression of the hematopoietic RUNX transcription factor lozenge and the subsequent production of crystal cells, which actuate the melanotic immune response in adult tsetse...
January 12, 2017: ELife
https://www.readbyqxmd.com/read/28077418/a-novel-humanized-mouse-model-with-significant-improvement-of-class-switched-antigen-specific-antibody-production
#20
Hua Yu, Chiara Borsotti, Jean-Nicolas Schickel, Shu Zhu, Till Strowig, Elizabeth E Eynon, Davor Frleta, Cagan Gurer, Andrew J Murphy, George D Yancopoulos, Eric Meffre, Markus G Manz, Richard A Flavell
Humanized mice are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, the existing models cannot support robust adaptive immune responses, especially the generation of class-switched, antigen-specific antibody responses. Here we describe a new mouse strain, in which human IL6 gene encoding the cytokine that is important for B and T cell differentiation was knocked into its respective mouse locus. The provision of human IL6 not only enhanced thymopoiesis and periphery T-cell engraftment, but also significantly increased class switched memory B cells and serum IgG...
January 11, 2017: Blood
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