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Erythropoiesis

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https://www.readbyqxmd.com/read/28737770/tissue-specific-ctcf-cohesin-mediated-chromatin-architecture-delimits-enhancer-interactions-and-function-in-vivo
#1
Lars L P Hanssen, Mira T Kassouf, A Marieke Oudelaar, Daniel Biggs, Chris Preece, Damien J Downes, Matthew Gosden, Jacqueline A Sharpe, Jacqueline A Sloane-Stanley, Jim R Hughes, Benjamin Davies, Douglas R Higgs
The genome is organized via CTCF-cohesin-binding sites, which partition chromosomes into 1-5 megabase (Mb) topologically associated domains (TADs), and further into smaller sub-domains (sub-TADs). Here we examined in vivo an ∼80 kb sub-TAD, containing the mouse α-globin gene cluster, lying within a ∼1 Mb TAD. We find that the sub-TAD is flanked by predominantly convergent CTCF-cohesin sites that are ubiquitously bound by CTCF but only interact during erythropoiesis, defining a self-interacting erythroid compartment...
July 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28736559/levocarnitine-injections-decrease-the-need-for-erythropoiesis-stimulating-agents-in-hemodialysis-patients-with-renal-anemia
#2
Takashi Maruyama, Terumi Higuchi, Toshio Yamazaki, Erina Okawa, Hideyuki Ando, Osamu Oikawa, Atsushi Inoshita, Kazuyoshi Okada, Masanori Abe
AIMS: The aim of this study was to evaluate the efficacy of levocarnitine injection for renal anemia in hemodialysis patients. METHODS: In this randomized controlled clinical trial, we randomly assigned patients on maintenance hemodialysis at our hospital to receive levocarnitine injections (n = 30) or no injection (n = 30) and monitored the patients during 12 months of treatment. In the treatment group, patients received an injection of levocarnitine 1,000 mg 3 times weekly after hemodialysis sessions...
June 2017: Cardiorenal Medicine
https://www.readbyqxmd.com/read/28736161/-immortalization-of-erythroid-progenitors-for-in-vitro-large-scale-red-cell-production
#3
A Caulier, L Guyonneau Harmand, L Garçon
Population ageing and increase in cancer incidence may lead to a decreased availability of red blood cell units. Thus, finding an alternative source of red blood cells is a highly relevant challenge. The possibility to reproduce in vitro the human erythropoiesis opens a new era, particularly since the improvement in the culture systems allows to produce erythrocytes from induced-Pluripotent Stem Cells (iPSCs), or CD34(+) Hematopoietic Stem Cells (HSCs). iPSCs have the advantage of in vitro self-renewal, but lead to poor amplification and maturation defects (high persistence of nucleated erythroid precursors)...
July 20, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28732065/direct-targets-of-pstat5-signalling-in-erythropoiesis
#4
Kevin R Gillinder, Hugh Tuckey, Charles C Bell, Graham W Magor, Stephen Huang, Melissa D Ilsley, Andrew C Perkins
Erythropoietin (EPO) acts through the dimeric erythropoietin receptor to stimulate proliferation, survival, differentiation and enucleation of erythroid progenitor cells. We undertook two complimentary approaches to find EPO-dependent pSTAT5 target genes in murine erythroid cells: RNA-seq of newly transcribed (4sU-labelled) RNA, and ChIP-seq for pSTAT5 30 minutes after EPO stimulation. We found 302 pSTAT5-occupied sites: ~15% of these reside in promoters while the rest reside within intronic enhancers or intergenic regions, some >100kb from the nearest TSS...
2017: PloS One
https://www.readbyqxmd.com/read/28730859/molecular-targeting-of-inosine-5-monophosphate-dehydrogenase-by-ff-10501-promotes-erythropoiesis-via-ros-mapk-pathway
#5
Michiko Ichii, Kenji Oritani, Motohiko Murase, Kensuke Komatsu, Mao Yamazaki, Rie Kyoden, Nobuko Kito, Yusuke Nozaki, Motoki Saito, Hiroyuki Iwamura, Yuzuru Kanakura
One of the major symptoms of myelodysplastic syndromes (MDS) is severe cytopenia. Despite cytokine therapies, such as erythropoiesis-stimulating agents, many patients still require blood transfusions, and the development of new therapeutic approaches is needed. In this work, we studied the effects of the inosine-5'-monophosphate (IMP) dehydrogenase (IMPDH) inhibitor FF-10501 on erythropoiesis of human hematopoietic cells. Differentiation of K562 chronic myeloid leukemia cells to an erythroid lineage was promoted by FF-10501 in a dose-dependent manner...
July 21, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28717990/iron-based-phosphate-binders-a-paradigm-shift-in-the-treatment-of-hyperphosphatemic-anemic-ckd-patients
#6
REVIEW
Francesco Locatelli, Lucia Del Vecchio
The partial correction of anemia and the normalization of phosphate and blood pressure are the mainstay of treatment of patients with chronic kidney disease (CKD). Available anti-hypertensive drugs, erythropoiesis stimulating agents (ESAs) and iron supplements have resolved quite satisfactorily the goal of controlling hypertension and partially correcting anemia. Unfortunately, the treatment of hyperphosphatemia is still far from resolved. Phosphate binders have poor tolerability and/or limited efficacy, leading to the prescription of many tablets that achieve only a mild-to-moderate effect...
July 17, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28717516/costs-associated-with-intravenous-darbepoetin-versus-epoetin-therapy-in-hemodialysis-patients-a-randomized-controlled-trial
#7
Andrea L Woodland, Sean W Murphy, Bryan M Curtis, Brendan J Barrett
BACKGROUND: Anemia of chronic kidney disease is associated with adverse outcomes and a reduced quality of life. Erythropoiesis-stimulating agents (ESAs) have improved anemia management, and 2 agents are available in Canada, epoetin alfa (EPO) and darbepoetin alfa (DA). EPO and DA are considered equally effective in achieving target hemoglobin (Hb), but it is not clear whether there is a cost difference. There have been few head-to-head comparisons; most published studies are observational switch studies...
2017: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/28716301/discrete-%C3%AE-adrenergic-mechanisms-regulate-early-and-late-erythropoiesis-in-erythropoietin-resistant-anemia
#8
Shirin Hasan, Michael J Mosier, Andrea Szilagyi, Richard L Gamelli, Kuzhali Muthumalaiappan
BACKGROUND: Anemia of critical illness is resistant to exogenous erythropoietin. Packed red blood cells transfusions is the only treatment option, and despite related cost and morbidity, there is a need for alternate strategies. Erythrocyte development can be divided into erythropoietin-dependent and erythropoietin-independent stages. We have shown previously that erythropoietin-dependent development is intact in burn patients and the erythropoietin-independent early commitment stage, which is regulated by β1/β2-adrenergic mechanisms, is compromised...
July 14, 2017: Surgery
https://www.readbyqxmd.com/read/28714517/overexpression-of-the-erythropoietin-receptor-in-rama-37-breast-cancer-cells-alters-cell-growth-and-sensitivity-to-tamoxifen
#9
Lenka Ilkovičová, Nina Trošt, Erika Szentpéteriová, Peter Solár, Radovan Komel, Nataša Debeljak
Erythropoietin (EPO) is the main regulator of erythropoiesis, and its receptor (EPOR) is expressed in various tissues, including tumors. Expression of EPOR in breast cancer tissue has been shown to correlate with expression of the estrogen receptor (ER). However, EPOR promotes proliferation in an EPO-independent manner. In patients with breast cancer, EPOR is associated with impaired tamoxifen response in ER-positive tumors, but not in ER-negative tumors. Furthermore, a positive correlation between EPOR/ER status and increased local cancer recurrence has been demonstrated, and EPOR expression is associated with G-protein coupled ER (GPER)...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28704831/reticulocyte-haemoglobin-content-declines-more-markedly-in-preterm-than-in-term-infants-in-the-first-days-after-birth
#10
Laila Lorenz, Andreas Peter, Jörg Arand, Fabian Springer, Christian F Poets, Axel R Franz
BACKGROUND: Reticulocyte haemoglobin content, i.e., the reticulocyte equivalent (Ret-He), seems to be a promising parameter for the detection of iron deficiency (ID) in neonates because it can be obtained as part of a reticulocyte count, with no additional blood loss and at no extra cost. Due to the short life span of reticulocytes, Ret-He reflects current iron availability for erythropoiesis more accurately than other common erythrocyte indices. OBJECTIVE: We aimed to evaluate postnatal changes in Ret-He within the first days after birth in term and preterm infants with the hypothesis that preterm infants experience a more pronounced postnatal reduction in Ret-He when compared to term infants...
July 14, 2017: Neonatology
https://www.readbyqxmd.com/read/28701754/clostridium-perfringens-%C3%AE-toxin-impairs-erythropoiesis-by-inhibition-of-erythroid-differentiation
#11
Teruhisa Takagishi, Masaya Takehara, Soshi Seike, Kazuaki Miyamoto, Keiko Kobayashi, Masahiro Nagahama
Clostridium perfringens α-toxin induces hemolysis of erythrocytes from various species, but it has not been elucidated whether the toxin affects erythropoiesis. In this study, we treated bone marrow cells (BMCs) from mice with purified α-toxin and found that TER119(+) erythroblasts were greatly decreased by the treatment. A variant α-toxin defective in enzymatic activities, phospholipase C and sphingomyelinase, had no effect on the population of erythroblasts, demonstrating that the decrease in erythroblasts was dependent of its enzymatic activities...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701737/circulating-primitive-erythroblasts-establish-a-functional-protein-4-1r-dependent-cytoskeletal-network-prior-to-enucleating
#12
Yu-Shan Huang, Luis F Delgadillo, Kathryn H Cyr, Paul D Kingsley, Xiuli An, Kathleen E McGrath, Narla Mohandas, John G Conboy, Richard E Waugh, Jiandi Wan, James Palis
Hematopoietic ontogeny is characterized by distinct primitive and definitive erythroid lineages. Definitive erythroblasts mature and enucleate extravascularly and form a unique membrane skeleton, composed of spectrin, 4.1R-complex, and ankyrinR-complex components, to survive the vicissitudes of the adult circulation. However, little is known about the formation and composition of the membrane skeleton in primitive erythroblasts, which progressively mature while circulating in the embryonic bloodstream. We found that primary primitive erythroblasts express the major membrane skeleton genes present in similarly staged definitive erythroblasts, suggesting that the composition and formation of this membrane network is conserved in maturing primitive and definitive erythroblasts despite their respective intravascular and extravascular locations...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28700957/a-protective-role-of-heme-regulated-eif2%C3%AE-kinase-in-cadmium-induced-liver-and-kidney-injuries
#13
Lixin Wang, Shuping Zhang, Zhe Wang, Ming Xu, Lin Yuan, Jiansheng Cui, Sijin Liu
A number of studies have reported that cadmium (Cd) can incur liver and kidney injuries. The recruitment and activation of leukocytes have been demonstrated to be involved in Cd-induced biological effects. Ironically, activated leukocytes and secreted cytokines are also reported to be required for the later recovery of the damaged tissues. Yet, the mechanisms driving the production of leukocytes have not been fully elucidated. Heme-regulated eIF2α kinase (HRI) is essential for translational regulation and stressed erythropoiesis in iron deficiency...
July 5, 2017: Chemosphere
https://www.readbyqxmd.com/read/28697999/the-protective-role-of-tet2-in-erythroid-iron-homeostasis-against-oxidative-stress-and-erythropoiesis
#14
Shanqi Guo, Xingkang Jiang, Yuanyuan Wang, Liwei Chen, Huzi Li, Xiaojiang Li, Yingjie Jia
Although previous studies suggested that stress erythropoiesis and iron metabolism regulate each other to increase iron availability for hemoglobin synthesis, the molecular bases determining its different traits remain elusive. In addition, global DNA demethylation has been reported during mouse erythropoiesis in vivo. However, the understanding of iron-related genes through DNA demethylation under stress erythropoiesis is largely unknown. In the current study, we found disordered iron homeostasis and misregulated hepcidin-ferroportin axis under stress erythropoiesis...
July 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28694211/novel-mutations-in-patients-with-hereditary-red-blood-cell-membrane-disorders-using-next-generation-sequencing
#15
Yunyan He, Siyuan Jia, Roma Kajal Dewan, Ning Liao
To diagnose and investigate the genotype-phenotype relationship in intractable hereditary red blood cell (RBC) membrane cases, we have utilized next-generation sequencing (NGS) to develop a high-throughput, highly sensitive assay. Three unrelated families including 15 individuals were analysed with a panel interrogating 600 genes related to haematopathy disorders. Where possible, inheritance patterns of pathogenic mutations were determined by sequencing the relatives. We identified 2 novel mutations in ANK1 (Y216X and E142X) responsible for hereditary spherocytosis (HS) that were stop-gain single nucleotide variants (SNVs)...
July 7, 2017: Gene
https://www.readbyqxmd.com/read/28694024/iron-metabolism-state-of-the-art
#16
R Daher, Z Karim
Iron homeostasis relies on the amount of its absorption by the intestine and its release from storage sites, the macrophages. Iron homeostasis is also dependent on the amount of iron used for the erythropoiesis. Hepcidin, which is synthesized predominantly by the liver, is the main regulator of iron metabolism. Hepcidin reduces serum iron by inhibiting the iron exporter, ferroportin expressed both tissues, the intestine and the macrophages. In addition, in the enterocytes, hepcidin inhibits the iron influx by acting on the apical transporter, DMT1...
July 7, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28685472/potential-erythropoiesis-in-the-primo-vascular-system-in-heart-failure
#17
Chae Jeong Lim, Yiming Shen, So Yeong Lee, Pan Dong Ryu
The primo-vascular system (PVS), composed of primo-nodes (PNs) and primo-vessels (PVs), has been identified in various animal models. However, little is known about its function. Here, we investigated the changes in gross morphology and cellular composition of the organ-surface PVS (osPVS) in rats with heart failure (HF) induced by myocardial infarction. The size of the PNs in rats with HF was larger than in sham rats (1.87 vs. 0.80 mm(2); P < 0.01) and the density of osPVS per rat was greater for the HF rats (28 of 6 rats vs...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28682312/the-bh3-only-proteins-bim-and-puma-are-not-critical-for-the-reticulocyte-apoptosis-caused-by-loss-of-the-pro-survival-protein-bcl-xl
#18
Alex Rd Delbridge, Brandon J Aubrey, Craig Hyland, Jonathan P Bernardini, Ladina Di Rago, Jean-Marc Garnier, Guillaume Lessene, Andreas Strasser, Warren S Alexander, Stephanie Grabow
Anaemia is a major global health problem arising from diverse causes and for which improved therapeutic strategies are needed. Erythroid cells can undergo apoptotic cell death and loss of pro-survival BCL-XL is known to trigger apoptosis during late-stage erythroid development. However, the mechanism by which loss or pharmacological blockade of BCL-XL leads to erythroid cell apoptosis remains unclear. Here we sought to identify the precise stage of erythropoiesis that depends on BCL-XL. We also tested whether deficiency of BIM or PUMA, the two main pro-apoptotic antagonists of BCL-XL, could prevent reticulocyte death and anaemia caused by BCL-XL loss...
July 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28682026/-clinical-management-of-anemia-in-patients-with-ckd
#19
Rodolfo Fernando Rivera, Maria Teresa Sciarrone Alibrandi, Luca Di Lullo, Fulvio Fioccari
Anemia is a frequent complication in chronic kidney disease (CKD), and it is often accompanied by various clinical symptoms. The primary cause of anemia in CKD patients is the reduction in the erythropoietin production, which results in a decrease of signaling molecule that stimulates red blood cell production. Other possible causes of anemia in CKD include iron deficiency, inflammation, and the accumulation of uremic toxin. This chapter focuses the discussion on the strategy of the management of anemia in patients with CKD...
March 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28679996/transcriptional-regulation-of-erythropoiesis
#20
Tohru Fujiwara
Hematopoietic cell differentiation is regulated by various lineage-specific transcription factors. In the context of erythroid differentiation, the importance of GATA-1 has been unequivocally demonstrated by cell-based ex vivo assays, as well as knockout mouse models and rare patients with anemias. GATA-1 regulates the expression of erythroid-related genes, such as globins and genes involved in heme biosynthesis, by recognizing the DNA binding consensus sequence [(A/T) GATA (A/G)] through dual zinc finger motifs...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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