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https://www.readbyqxmd.com/read/29442367/no-strict-requirement-for-eosinophils-for-bone-marrow-plasma-cell-survival
#1
Alexandra Bortnick, Irene Chernova, Sean P Spencer, David Allman
Lasting antibody responses are maintained by long-lived plasma cells, which are thought to lodge in the bone marrow (BM) in specialized survival niches. Eosinophils have been reported to function as a critical component of the BM survival niche where they are thought to provide pro-survival signals to nearby plasma cells. Recent work shows that many BM plasma cells are recently generated and chiefly short-lived cells, raising the possibility that rare plasma cell-eosinophil interactions are a rate-limiting step needed to establish lasting humoral immunity...
February 14, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29435140/triplications-of-human-chromosome-21-orthologous-regions-in-mice-result-in-expansion-of-megakaryocyte-erythroid-progenitors-and-reduction-of-granulocyte-macrophage-progenitors
#2
Chunhong Liu, Tao Yu, Zhuo Xing, Xiaoling Jiang, Yichen Li, Annie Pao, Justin Mu, Paul K Wallace, George Stoica, Andrei V Bakin, Y Eugene Yu
Individuals with Down syndrome (DS) frequently have hematopoietic abnormalities, including transient myeloproliferative disorder and acute megakaryoblastic leukemia which are often accompanied by acquired GATA1 mutations that produce a truncated protein, GATA1s. The mouse has been used for modeling DS based on the syntenic conservation between human chromosome 21 (Hsa21) and three regions in the mouse genome located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. To assess the impact of the dosage increase of Hsa21 gene orthologs on the hematopoietic system, we characterized the related phenotype in the Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+ model which carries duplications spanning the entire Hsa21 orthologous regions on Mmu10, Mmu16 and Mmu17, and the Dp(10)1Yey /+; Dp(16)1Yey /+; Dp(17)1Yey/+ ; Gata1 Yeym2 model which carries a Gata1s mutation we engineered...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29417230/identification-of-megakaryocytes-as-a-target-of-advanced-glycation-end-products-in-diabetic-complications-in-bone-marrow
#3
Benfang Wang, Jianjiang Yu, Ting Wang, Ying Shen, Dandan Lin, Xin Xu, Yiqiang Wang
AIMS: To define the possible effect of diabetic conditions on megakaryocytes, the long-know precursors of platelets and lately characterized modulator of hematopoietic stem quiescence-activation transition. METHODS: Megakaryoblastic MEG-01 cell culture and TPO/SCF/IL-3-induced differentiation of human umbilical blood mononuclear cells toward megakaryocytes were used to test effects of glycated bovine serum albumin (BSA-AGEs). The ob/ob mice and streptozotocin-treated mice were used as models of hyperglycemia...
February 8, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29408805/ribonuclease-inhibitor-1-regulates-erythropoiesis-by-controlling-gata1-mrna-translation
#4
Vijaykumar Chennupati, Diogo Ft Veiga, Kendle M Maslowski, Nicola Andina, Aubry Tardivel, Eric Chi-Wang Yu, Martina Stilinovic, Cedric Simillion, Michel A Duchosal, Manfredo Quadroni, Irene Roberts, Vijay G Sankaran, H Robson MacDonald, Nicolas Fasel, Anne Angelillo-Scherrer, Pascal Schneider, Trang Hoang, Ramanjaneyulu Allam
Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anaemia and 5q- syndrome, mutations in RP genes lead to a specific defect in erythroid gene translation and cause anaemia. Little is known about the molecular mechanisms of selective mRNA translation and involvement of ribosomal-associated factors in this process. Ribonuclease inhibitor (RNH1) is an ubiquitously expressed protein that binds to and inhibits pancreatic-type ribonucleases...
February 6, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29400094/gata1-insufficiencies-in-primary-myelofibrosis-and-other-hematopoietic-disorders-consequences-for-therapy
#5
Te Ling, John D Crispino, Maria Zingariello, Fabrizio Martelli, Anna Rita Migliaccio
GATA1, the founding member of a family of transcription factors, plays important roles in the development of hematopoietic cells of several lineages. Although loss of GATA1 has been known to impair hematopoiesis in animal models for nearly 25 years, the link between GATA1 defects and human blood diseases has only recently been realized. Areas covered: Here the current understanding of the functions of GATA1 in normal hematopoiesis and how it is altered in disease is reviewed. GATA1 is indispensable mainly for erythroid and megakaryocyte differentiation...
February 5, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29389946/the-effect-of-histone-deacetylase-inhibitors-on-ahsp-expression
#6
Mohammad Ali Okhovat, Katayoun Ziari, Reza Ranjbaran, Negin Nikouyan
Alpha-hemoglobin stabilizing protein (AHSP) is a molecular chaperone that can reduce the damage caused by excess free α-globin to erythroid cells in patients with impaired β-globin chain synthesis. We assessed the effect of sodium phenylbutyrate and sodium valproate, two histone deacetylase inhibitors (HDIs) that are being studied for the treatment of hemoglobinopathies, on the expression of AHSP, BCL11A (all isoforms), γ-globin genes (HBG1/2), and some related transcription factors including GATA1, NFE2, EKLF, KLF4, and STAT3...
2018: PloS One
https://www.readbyqxmd.com/read/29382819/rassf1a-uncouples-wnt-from-hippo-signalling-and-promotes-yap-mediated-differentiation-via-p73
#7
Angelos Papaspyropoulos, Leanne Bradley, Asmita Thapa, Chuen Yan Leung, Konstantinos Toskas, Delia Koennig, Dafni-Eleftheria Pefani, Cinzia Raso, Claudia Grou, Garth Hamilton, Nikola Vlahov, Anna Grawenda, Syed Haider, Jagat Chauhan, Ludovico Buti, Alexander Kanapin, Xin Lu, Francesca Buffa, Grigory Dianov, Alex von Kriegsheim, David Matallanas, Anastasia Samsonova, Magdalena Zernicka-Goetz, Eric O'Neill
Transition from pluripotency to differentiation is a pivotal yet poorly understood developmental step. Here, we show that the tumour suppressor RASSF1A is a key player driving the early specification of cell fate. RASSF1A acts as a natural barrier to stem cell self-renewal and iPS cell generation, by switching YAP from an integral component in the β-catenin-TCF pluripotency network to a key factor that promotes differentiation. We demonstrate that epigenetic regulation of the Rassf1A promoter maintains stemness by allowing a quaternary association of YAP-TEAD and β-catenin-TCF3 complexes on the Oct4 distal enhancer...
January 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29377892/network-based-co-expression-analysis-for-exploring-the-potential-diagnostic-biomarkers-of-metastatic-melanoma
#8
Li-Xin Wang, Yang Li, Guan-Zhi Chen
Metastatic melanoma is an aggressive skin cancer and is one of the global malignancies with high mortality and morbidity. It is essential to identify and verify diagnostic biomarkers of early metastatic melanoma. Previous studies have systematically assessed protein biomarkers and mRNA-based expression characteristics. However, molecular markers for the early diagnosis of metastatic melanoma have not been identified. To explore potential regulatory targets, we have analyzed the gene microarray expression profiles of malignant melanoma samples by co-expression analysis based on the network approach...
2018: PloS One
https://www.readbyqxmd.com/read/29321178/transcription-factor-dependent-anti-repressive-mammalian-enhancers-exclude-h3k27me3-from-extended-genomic-domains
#9
Madhurima Saxena, Adrianna K San Roman, Nicholas K O'Neill, Rita Sulahian, Unmesh Jadhav, Ramesh A Shivdasani
Compacted chromatin and nucleosomes are known barriers to gene expression; the nature and relative importance of other transcriptional constraints remain unclear, especially at distant enhancers. Polycomb repressor complex 2 (PRC2) places the histone mark H3K27me3 predominantly at promoters, where its silencing activity is well documented. In adult tissues, enhancers lack H3K27me3, and it is unknown whether intergenic H3K27me3 deposits affect nearby genes. In primary intestinal villus cells, we identified hundreds of tissue-restricted enhancers that require the transcription factor (TF) CDX2 to prevent the incursion of H3K27me3 from adjoining areas of elevated basal marking into large well-demarcated genome domains...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29317231/the-ancient-role-for-gata2-3-transcription-factor-homolog-in-the-hemocyte-production-of-oyster
#10
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
#11
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/29296843/the-severe-phenotype-of-diamond-blackfan-anemia-is-modulated-by-heat-shock-protein-70
#12
Marc Gastou, Sarah Rio, Michaël Dussiot, Narjesse Karboul, Hélène Moniz, Thierry Leblanc, Margaux Sevin, Patrick Gonin, Jérome Larghéro, Carmen Garrido, Anupama Narla, Narla Mohandas, William Vainchenker, Olivier Hermine, Eric Solary, Lydie Da Costa
Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome that exhibits an erythroid-specific phenotype. In at least 70% of cases, DBA is related to a haploinsufficient germ line mutation in a ribosomal protein (RP) gene. Additional cases have been associated with mutations in GATA1. We have previously established that the RPL11 +/Mut phenotype is more severe than RPS19 +/Mut phenotype because of delayed erythroid differentiation and increased apoptosis of RPL11 +/Mut erythroid progenitors...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29247537/gata1-activated-lncrna-galont-promotes-anoxia-reoxygenation-induced-autophagy-and-cell-death-in-cardiomyocytes-by-sponging-mir-338
#13
Guotian Yin, Xiuli Yang, Qiong Li, Zhikun Guo
The hypernomic autophagy is associated with various cardiovascular diseases. Long noncoding RNAs (lncRNAs) are emerging as important regulators in gene expression, which have been involved in multiple physiological and pathological processes. However, the function of lncRNAs and how they functioned in the autophagy in cardiomyocytes were rarely reported. In this study, we report that a lncRNA, named GATA1 activated lncRNA (Galont), can directly interact with miR-338 and promote ATG5-mediated autophagic cell death in murine cardiomyocytes...
December 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29174036/increase-in-renal-erythropoietin-receptors-in-diabetic-rats-is-mainly-mediated-by-hyperglycemia-associated-with-the-stat3-gata-1-signaling-pathway
#14
Shu-Chun Kuo, Yingxiao Li, Kai-Chun Cheng, Chiang-Shan Niu, Juei-Tang Cheng, Ho-Shan Niu
Erythropoietin (EPO) produces cytoprotection in many tissues by activating the EPO receptor (EPOR); these effects include anti-oxidative stress and the inhibition of apoptosis in renal tubular cells. Moreover, EPO is clinically used in diabetic patients who suffer from chronic renal disease. However, the effect of hyperglycemia on renal EPOR expression remains unknown. Therefore, we determined the changes in renal EPOR expression in diabetic rats and investigated the role of potential factors using cultured cells...
November 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29137279/implications-of-mutational-spectrum-in-myelodysplastic-syndromes-based-on-targeted-next-generation-sequencing
#15
Yuanyuan Xu, Yan Li, Qingyu Xu, Yuelong Chen, Na Lv, Yu Jing, Liping Dou, Jian Bo, Guangyuan Hou, Jing Guo, Xiuli Wang, Lili Wang, Yonghui Li, Chongjian Chen, Li Yu
Myelodysplastic syndromes (MDS) are a group of myeloid hematological malignancies, with a high risk of progression to acute myeloid leukemia (AML). To explore the role of acquired mutations in MDS, 111 MDS-associated genes were screened using next-generation sequencing (NGS), in 125 patients. One or more mutations were detected in 84% of the patients. Some gene mutations are specific for MDS and were associated with disease subtypes, and the patterns of mutational pathways could be associated with progressive MDS...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29110609/bmp3-is-required-for-integrity-of-blood-brain-barrier-by-promoting-pericyte-coverage-in-zebrafish-embryos
#16
D Lei, X Jin, L Wen, H Dai, Z Ye, G Wang
BACKGROUND: The compromise of blood brain barrier (BBB) integrity is often associated with human hemorrhage stroke and neurodegeneration diseases, including retina diseases, such as age-related macular degeneration and diabetic retinopathy. Brain pericytes play pivotal roles in regulation and maintenance of BBB integrity. However, the mechanisms underlying brain pericyte development to establish BBB integrity remain unclear. METHODS: zebrafish transgenic lines Tg(flk1:GFP; gata1:dsRed), Tg(flk1:GFP), Tg(fli1:GFP) and Tg(BRE:GFP) were used in this work...
November 5, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29074889/unravelling-pathways-downstream-sox6-induction-in-k562-erythroid-cells-by-proteomic-analysis
#17
Gloria Barbarani, Antonella Ronchi, Margherita Ruoppolo, Lucia Santorelli, Robert Steinfelder, Sudharshan Elangovan, Cristina Fugazza, Marianna Caterino
The Sox6 transcription factor is crucial for terminal maturation of definitive red blood cells. Sox6-null mouse fetuses present misshapen and nucleated erythrocytes, due to impaired actin assembly and cytoskeleton stability. These defects are accompanied with a reduced survival of Sox6(-/-) red blood cells, resulting in a compensated anemia. Sox6-overexpression in K562 cells and in human primary ex vivo erythroid cultures enhances erythroid differentiation and leads to hemoglobinization, the hallmark of erythroid maturation...
October 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29069738/hematopoietic-transcription-factors-and-differential-cofactor-binding-regulate-prkacb-isoform-expression
#18
Olga N Kuvardina, Stefanie Herkt, Annekarin Meyer, Lucas Schneider, Jasmin Yillah, Nicole Kohrs, Halvard Bonig, Erhard Seifried, Carsten Müller-Tidow, Jörn Lausen
Hematopoietic differentiation is controlled by key transcription factors, which regulate stem cell functions and differentiation. TAL1 is a central transcription factor for hematopoietic stem cell development in the embryo and for gene regulation during erythroid/megakaryocytic differentiation. Knowledge of the target genes controlled by a given transcription factor is important to understand its contribution to normal development and disease. To uncover direct target genes of TAL1 we used high affinity streptavidin/biotin-based chromatin precipitation (Strep-CP) followed by Strep-CP on ChIP analysis using ChIP promoter arrays...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29031773/identification-of-cdan1-c15orf41-and-sec23b-mutations-in-chinese-patients-affected-by-congenital-dyserythropoietic-anemia
#19
Yongwei Wang, Yongxin Ru, Gang Liu, Shuxu Dong, Yuan Li, Xiaofan Zhu, Fengkui Zhang, Yan-Zhong Chang, Guangjun Nie
Congenital dyserythropoietic anaemias (CDAs) are a group of rare haematological disorders characterized by ineffective erythropoiesis and dyserythropoiesis and reduced numbers of red cells, often with an abnormal morphology. Pathogenic defects in CDAN1, C15ORF41, SEC23B, KIF23, KLF1 and GATA1 genes have been identified in CDAs patients. In this study, we described 13 unrelated Chinese CDAs patients and identified 21 mutations, including 5 novel mutations in CDAN1 gene, and 5 novel mutations in SEC23B gene. Additionally, we predicted the molecular consequence of these missense mutations with Polymorphism Phenotyping v2 (Polyphen), Sorting Intolerant From Tolerant (SIFT), MutPred (http://mutpred1...
January 15, 2018: Gene
https://www.readbyqxmd.com/read/28986286/differential-responses-of-lineages-committed-hematopoietic-progenitors-and-altered-expression-of-self-renewal-and-differentiation-related-genes-in-1-4-benzoquinone-1-4-bq-exposure
#20
Paik Wah Chow, Nor Fadilah Rajab, Kien Hui Chua, Kok Meng Chan, Zariyantey Abd Hamid
Despite of reports on hematotoxic and leukemogenic evidences related to benzene exposure, the mechanism of benzene toxicity affecting the hematopoietic stem and progenitor cells (HSPCs) fate remains unclear. This study aims to elucidate the benzene's effect on the lineages-committed progenitors and genes-regulating self-renewal and differentiation of HSPCs. Isolated mouse bone marrow (BM) cells were exposed to the benzene metabolite, 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, and 5μM for 24h. The clonogenic potency of erythroid, myeloid, and Pre-B lymphoid progenitors was evaluated through colony-forming-cell assay...
October 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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