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https://www.readbyqxmd.com/read/29343653/establishment-of-a-screening-system-to-identify-novel-gata-2-transcriptional-regulators
#1
Keiichi Ohashi, Tohru Fujiwara, Koichi Onodera, Yo Saito, Satoshi Ichikawa, Masahiro Kobayashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Hideo Harigae
Hematopoietic stem cells can self-renew and differentiate into all blood cell types. The transcription factor GATA-2 is expressed in hematopoietic stem and progenitor cells and is essential for cell proliferation and differentiation. Heterozygous germline GATA2 mutations induce GATA-2 deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia and acute myeloid leukemia, and a profoundly reduced dendritic cell (DC) population, which is associated with increased susceptibility to viral infections...
2018: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29317231/the-ancient-role-for-gata2-3-transcription-factor-homolog-in-the-hemocyte-production-of-oyster
#2
Xiaorui Song, Xiaoyu Xin, Miren Dong, Weilin Wang, Lingling Wang, Linsheng Song
Hemocytes, the cellular component of invertebrate hemolymph, are essential for invertebrate immunity, but the hematopoiesis and regulation mechanism are still largely unknown. In the present study, a conserved hematopoietic transcription factor Cg-GATA2/3 was identified in Pacific oyster Crassotrea gigas, which was evolutionarily close to the vertebrate GATA1/2/3. Cg-GATA2/3 was mainly distributed in the immune organs, such as gill, hemocytes, and mantle. After Cg-GATA2/3 was interferenced by dsRNA, the mRNA expressions of hemocytes specific gene (EcSOD) and hematopoietic transcription factor (C-Myb) were all significant down-regulated, and the hemocyte renewal rates also decreased both in hemolymph and gill...
January 6, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29302254/terminally-differentiating-eosinophils-express-neutrophil-primary-granule-proteins-as-well-as-eosinophil-specific-granule-proteins-in-a-temporal-manner
#3
Karam Kim, Sae Mi Hwang, Sung Min Kim, Sung Woo Park, Yunjae Jung, Il Yup Chung
Neutrophils and eosinophils, 2 prominent granulocytes, are commonly derived from myelocytic progenitors through successive stages in the bone marrow. Our previous genome-wide transcriptomic data unexpectedly showed that genes encoding a multitude of neutrophil primary granule proteins (NPGPs) were markedly downregulated during the end period of eosinophilic terminal differentiation when cord blood (CB) cluster of differentiation (CD) 34+ cells were induced to differentiate toward the eosinophil lineage during a 24-day culture period...
December 2017: Immune Network
https://www.readbyqxmd.com/read/29296959/somatic-mutations-in-children-with-gata2-associated-myelodysplastic-syndrome-who-lack-other-features-of-gata2-deficiency
#4
Kevin E Fisher, Amy P Hsu, Christopher L Williams, Hadi Sayeed, Brian Y Merritt, M Tarek Elghetany, Steven M Holland, Alison A Bertuch, Maria Monica Gramatges
Approximately 10% of children with primary myelodysplastic syndrome (MDS) have germ line GATA2 mutations, leading to the proposal that all children with primary MDS and certain cytogenetic findings, including monosomy 7, be tested for germ line GATA2 mutations regardless of family history or other clinical features associated with GATA2 deficiency. In adults with familial GATA2-MDS, those with somatic mutations in ASXL1 experience rapid disease progression to acute myeloid leukemia (AML) and poor prognosis after stem cell transplantation; however, the prevalence of somatic mutations in primary pediatric GATA2-MDS is unclear...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296814/twist1-regulates-embryonic-hematopoietic-differentiation-through-binding-to-myb-and-gata2-promoter-regions
#5
Kasem Kulkeaw, Tomoko Inoue, Tadafumi Iino, Kenzaburo Tani, Koichi Akashi, Nancy A Speck, Yoichi Nakanishi, Daisuke Sugiyama
Mechanisms underlying differentiation of embryonic hematopoietic stem/progenitor cells (HSPCs) remain unclear. In mouse, intra-aortic clusters (IACs) form in the aorta-gonad-mesonephros region and acquire HSPC potential after 9.5 days postcoitum (dpc). In this study we demonstrate that Twist1 is highly expressed in c-Kit+CD31+CD34+ IACs, which are equivalent to embryonic HSPCs, compared with adult HSPCs. Progenitor activities of colony-forming unit (CFU) of granulocytes and macrophages, CFU of macrophages, burst-forming unit of erythroid, and B lymphopoiesis were impaired in IACs of Twist1-/- relative to wild-type embryos...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295841/in-vivo-t-depleted-reduced-intensity-transplantation-for-gata2-related-immune-dysfunction
#6
Eleni Tholouli, Katherine Sturgess, Rachel E Dickinson, Andrew Gennery, Andrew J Cant, Graham Jackson, Jim Lordan, Sophie Hambleton, Mary A Slatter, Venetia Bigley, Matthew Collin
No abstract text is available yet for this article.
January 2, 2018: Blood
https://www.readbyqxmd.com/read/29277702/the-transcription-factors-gata2-and-mitf-regulate-hdc-gene-expression-in-mast-cells-and-are-required-for-ige-mast-cell-mediated-anaphylaxis
#7
Yapeng Li, Bing Liu, Laura Harmacek, Zijie Long, Jinyi Liang, Kara Lukin, Sonia M Leach, Brian O'Connor, Anthony N Gerber, James Hagman, Axel Roers, Fred D Finkelman, Hua Huang
BACKGROUND: Histamine is a critical mediator of IgE/mast cell-mediated anaphylaxis. Histamine is synthesized by decarboxylating the amino acid histidine, a reaction catalyzed by the Hdc-gene encoded enzyme histidine decarboxylase. However, regulation of the Hdc gene in mast cells is poorly understood. OBJECTIVE: We sought to investigate the in vivo regulation of IgE/mast cell mediated anaphylaxis by transcription factors GATA2 and MITF and the mechanisms by which GATA2 and MITF regulate Hdc gene expression in mouse and human mast cells...
December 22, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29276152/in%C3%A2-vitro-differentiation-of-gata2-and-ly6a-reporter-embryonic-stem-cells-corresponds-to-in%C3%A2-vivo-waves-of-hematopoietic-cell-generation
#8
Mari-Liis Kauts, Carmen Rodriguez-Seoane, Polynikis Kaimakis, Sandra C Mendes, Xabier Cortés-Lavaud, Undine Hill, Elaine Dzierzak
In vivo hematopoietic generation occurs in waves of primitive and definitive cell emergence. Differentiation cultures of pluripotent embryonic stem cells (ESCs) offer an accessible source of hematopoietic cells for blood-related research and therapeutic strategies. However, despite many approaches, it remains a goal to robustly generate hematopoietic progenitor and stem cells (HP/SCs) in vitro from ESCs. This is partly due to the inability to efficiently promote, enrich, and/or molecularly direct hematopoietic emergence...
December 15, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29275211/up-regulation-of-pomc-and-cart-mrnas-by-intermittent-hypoxia-via-gata-transcription-factors-in-human-neuronal-cells
#9
Ryogo Shobatake, Ken Takasawa, Hiroyo Ota, Asako Itaya-Hironaka, Akiyo Yamauchi, Sumiyo Sakuramoto-Tsuchida, Tomoko Uchiyama, Mai Makino, Kazuma Sugie, Shin Takasawa, Satoshi Ueno
Sleep apnea syndrome (SAS) is characterized by intermittent hypoxia (IH) during sleep. SAS and obesity are strongly related to each other. Here, we investigated the effect of IH on the expression of major appetite regulatory genes in human neuronal cells. We exposed NB-1, SH-SY5Y, and SK-N-SH human neuronal cells to IH (64 cycles of 5 min hypoxia and 10 min normoxia), normoxia, or sustained hypoxia for 24 h and measured the mRNA levels of proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), galanin, galanin-like peptide, ghrelin, pyroglutamylated RFamide peptide, agouti-related peptide, neuropeptide Y, and melanocortin 4 receptor by real-time RT-PCR...
December 21, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29249045/longitudinal-patterning-in-roots-a-gata2-auxin-interaction-underlies-and-maintains-the-root-transition-domain
#10
Keni Jiang, Vincent Yung, Taisei Chiba, Lewis J Feldman
In Arabidopsis thaliana root meristems the GATA2 transcription factor is a marker for the root transition domain, is auxin regulated, and functions to restrict cell division activity. The growing part of roots is comprised of three discrete regions; the proliferative domain (PD), an elongation zone, and interposed between these two, the transition domain (TD), which is the focus of this investigation. Within the TD, it is hypothesized that cells are reprogrammed, losing the capacity to divide and begin to differentiate...
December 16, 2017: Planta
https://www.readbyqxmd.com/read/29230432/case-report-of-an-adolescent-male-with-unexplained-pancytopenia-gata2-associated-bone-marrow-failure-and-genetic-testing
#11
Lauren Azevedo, Allison Jay, Adonis Lorenzana, Sioban Keel, Roshini S Abraham, Marshall Horwitz, Michelle van Hee, Hadi Sawaf
No abstract text is available yet for this article.
2017: Global Pediatric Health
https://www.readbyqxmd.com/read/29227476/the-molecular-landscape-of-pediatric-acute-myeloid-leukemia-reveals-recurrent-structural-alterations-and-age-specific-mutational-interactions
#12
Hamid Bolouri, Jason E Farrar, Timothy Triche, Rhonda E Ries, Emilia L Lim, Todd A Alonzo, Yussanne Ma, Richard Moore, Andrew J Mungall, Marco A Marra, Jinghui Zhang, Xiaotu Ma, Yu Liu, Yanling Liu, Jaime M Guidry Auvil, Tanja M Davidsen, Patee Gesuwan, Leandro C Hermida, Bodour Salhia, Stephen Capone, Giridharan Ramsingh, Christian Michel Zwaan, Sanne Noort, Stephen R Piccolo, E Anders Kolb, Alan S Gamis, Malcolm A Smith, Daniela S Gerhard, Soheil Meshinchi
We present the molecular landscape of pediatric acute myeloid leukemia (AML) and characterize nearly 1,000 participants in Children's Oncology Group (COG) AML trials. The COG-National Cancer Institute (NCI) TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG methylation profiling. Validated DNA variants corresponded to diverse, infrequent mutations, with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including new gene fusions and focal deletions of MBNL1, ZEB2 and ELF1, were disproportionately prevalent in young individuals as compared to adults...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29222240/old-and-new-tools-in-the-clinical-diagnosis-of-inherited-bone-marrow-failure-syndromes
#13
REVIEW
Allison H West, Jane E Churpek
Patients with inherited bone marrow failure syndromes (IBMFSs) classically present with specific patterns of cytopenias along with congenital anomalies and/or other physical features that are often recognizable early in life. However, increasing application of genomic sequencing and clinical awareness of subtle disease presentations have led to the recognition of IBMFS in pediatric and adult populations more frequently than previously realized, such as those with early onset myelodysplastic syndrome (MDS). Given the well-defined differences in clinical management needs and outcomes for aplastic anemia, acute myeloid leukemia, and MDS in patients with an IBMFS vs those occurring sporadically, as well as nonhematologic comorbidities in patients with IBMFSs, it is critical for hematologists to understand how to approach screening for the currently known IBMFSs...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221486/a-screening-system-to-identify-transcription-factors-that-induce-binding-site-directed-dna-demethylation
#14
Takahiro Suzuki, Shiori Maeda, Erina Furuhata, Yuri Shimizu, Hajime Nishimura, Mami Kishima, Harukazu Suzuki
BACKGROUND: DNA methylation is a fundamental epigenetic modification that is involved in many biological systems such as differentiation and disease. We and others recently showed that some transcription factors (TFs) are involved in the site-specific determination of DNA demethylation in a binding site-directed manner, although the reports of such TFs are limited. RESULTS: Here, we develop a screening system to identify TFs that induce binding site-directed DNA methylation changes...
December 8, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29217535/in-vivo-single-cell-analysis-reveals-gata2-dynamics-in-cells-transitioning-to-hematopoietic-fate
#15
Christina Eich, Jochen Arlt, Chris S Vink, Parham Solaimani Kartalaei, Polynikis Kaimakis, Samanta A Mariani, Reinier van der Linden, Wiggert A van Cappellen, Elaine Dzierzak
Cell fate is established through coordinated gene expression programs in individual cells. Regulatory networks that include the Gata2 transcription factor play central roles in hematopoietic fate establishment. Although Gata2 is essential to the embryonic development and function of hematopoietic stem cells that form the adult hierarchy, little is known about the in vivo expression dynamics of Gata2 in single cells. Here, we examine Gata2 expression in single aortic cells as they establish hematopoietic fate in Gata2Venus mouse embryos...
December 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29197497/delta-like-homolog1-gata-binding-protein-2-axis-mediates-leptin-inhibition-of-ppar%C3%AE-2-expression-in-hepatic-stellate-cells-in-vitro
#16
Yuanyuan Cheng, Xiaofei Zhu, Fangyun Cheng, Li Ji, Yajun Zhou
AIMS: Peroxisome-proliferator activated receptor γ (PPARγ) plays a pivotal role in inhibition of hepatic stellate cell (HSC) activation, a key step for liver fibrogenesis. Adipocyte-derived hormone leptin has been shown to promote liver fibrosis in murine and human. PPARγ includes two subtypes, PPARγ1 and PPARγ2. Our previous study indicated that leptin down-regulated PPARγ1 expression in HSCs. The aim of this study was to investigate the effect of leptin on PPARγ2 expression and the underlying mechanisms in HSCs...
November 29, 2017: Life Sciences
https://www.readbyqxmd.com/read/29189513/successful-nonmyeloablative-allogeneic-stem-cell-transplant-in-a-child-with-emberger-syndrome-and-gata2-mutation
#17
Neha Rastogi, Roshini S Abraham, Ritu Chadha, Dhwanee Thakkar, Shruti Kohli, Sagar Nivargi, Satya Prakash Yadav
Emberger syndrome with underlying guanine-adenine-thymine-adenine 2 (GATA2) mutation is a rare disorder and very few successful nonmyeloablative allogeneic hematopoietic stem cell transplants (HSCTs) have been reported. We report a case of Emberger syndrome with GATA2 mutation in a 9-year-old girl who presented with congenital sensorineural deafness, warts, lymphedema, and Myelodysplastic syndrome. Her sister had died of a similar illness. She underwent a nonmyeloablative matched related donor peripheral blood HSCT with rabbit antithymoglobulin (5 mg/kg), fludarabine (160 mg/m), cyclophophamide (29 mg/kg), and total body irradiation (2 Gray)...
November 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29156748/association-of-melatonin-membrane-receptor-1a-1b-gene-polymorphisms-with-the-occurrence-and-metastasis-of-hepatocellular-carcinoma
#18
Shih-Chi Su, Yung-Chuan Ho, Yu-Fan Liu, Russel J Reiter, Chia-Hsuan Chou, Chia-Ming Yeh, Hsiang-Lin Lee, Wen-Hung Chung, Ming-Ju Hsieh, Shun-Fa Yang
Hepatocellular carcinoma (HCC) is a prevalent primary neoplasm of the liver, whose heterogeneous global incidence suggests the likely impact of genetic variations among individuals on the susceptibility to this disease. Increasing evidence indicates that melatonin exhibits oncostatic properties in many cancer types at least in part mediated by its membrane-bound receptors, melatonin receptor 1A (encoded by MTNR1A) and 1B (MTNR1B). In this study, the effect of melatonin receptor gene polymorphisms on the risk and progression of hepatic tumors was evaluated between 335 HCC patients and 1196 cancer-free subjects...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156497/melanoma-in-patients-with-gata2-deficiency
#19
Jannett Nguyen, Tiffany Alexander, Hong Jiang, Natasha Hill, Zied Abdullaev, Svetlana D Pack, Amy P Hsu, Steven M Holland, Dennis D Hickstein, Eric A Engels, Isaac Brownell
GATA2 deficiency is a recently described genetic disorder affecting hematopoietic stem cells and is associated with immunodeficiency, cutaneous findings, and hematologic malignancy. The risk of non-hematologic malignancies is unclear. To explore the incidence and clinical course of melanoma in GATA2 deficient patients we conducted a retrospective chart review of 71 patients with GATA2 deficiency. We identified two patients with melanoma, including an invasive melanoma presenting as a graft-versus-tumor effect following bone marrow transplantation...
November 20, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29146883/a-landscape-of-germline-mutations-in-a-cohort-of-inherited-bone-marrow-failure-patients
#20
Olivier Bluteau, Marie Sebert, Thierry Leblanc, Régis Peffault de Latour, Samuel Quentin, Elodie Lainey, Lucie Hernandez, Jean-Hugues Dalle, Flore Sicre de Fontbrune, Etienne Lengline, Raphael Itzykson, Emmanuelle Clappier, Nicolas Boissel, Naddia Vasquez, Mélanie Da Costa, Julien Masliah-Planchon, Wendy Cuccuini, Anna Raimbault, Louis De Jaegere, Lionel Adès, Pierre Fenaux, Sébastien Maury, Claudine Schmitt, Marc Muller, Carine Domenech, Nicolas Blin, Bénédicte Bruno, Isabelle Pellier, Mathilde Hunault, Stéphane Blanche, Arnaud Petit, Guy Leverger, Gérard Michel, Yves Bertrand, André Baruchel, Gérard Socié, Jean Soulier
Bone marrow failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% bone marrow blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germline mutation in 86 patients (48...
November 16, 2017: Blood
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