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  1 / 2919 MEDLINE  
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[PMID]:28916711
[Au] Autor:Huang P; Keller CA; Giardine B; Grevet JD; Davies JOJ; Hughes JR; Kurita R; Nakamura Y; Hardison RC; Blobel GA
[Ad] Endereço:Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
[Ti] Título:Comparative analysis of three-dimensional chromosomal architecture identifies a novel fetal hemoglobin regulatory element.
[So] Source:Genes Dev;31(16):1704-1713, 2017 Aug 15.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chromatin structure is tightly intertwined with transcription regulation. Here we compared the chromosomal architectures of fetal and adult human erythroblasts and found that, globally, chromatin structures and compartments A/B are highly similar at both developmental stages. At a finer scale, we detected distinct folding patterns at the developmentally controlled ß-globin locus. Specifically, new fetal stage-specific contacts were uncovered between a region separating the fetal (γ) and adult (δ and ß) globin genes (encompassing the and noncoding genes) and two distal chromosomal sites (HS5 and 3'HS1) that flank the locus. In contrast, in adult cells, the - region contacts the embryonic ε-globin gene, physically separating the fetal globin genes from the enhancer (locus control region [LCR]). Deletion of the region in adult cells alters contact landscapes in ways more closely resembling those of fetal cells, including increased LCR-γ-globin contacts. These changes are accompanied by strong increases in γ-globin transcription. Notably, the effects of removal on chromatin architecture and gene expression closely mimic those of deleting the fetal globin repressor BCL11A, implicating BCL11A in the function of the region. Our results uncover a new critical regulatory region as a potential target for therapeutic genome editing for hemoglobinopathies and highlight the power of chromosome conformation analysis in discovering new control elements.
[Mh] Termos MeSH primário: Cromatina/química
Eritroblastos/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Elementos Reguladores de Transcrição
Globinas beta/genética
[Mh] Termos MeSH secundário: Adulto
Proteínas de Transporte/genética
Feto
Inativação Gênica
Seres Humanos
Região de Controle de Locus Gênico
Proteínas Nucleares/genética
Pseudogenes
Transcriptoma
gama-Globinas/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BCL11A protein, human); 0 (Carrier Proteins); 0 (Chromatin); 0 (Nuclear Proteins); 0 (beta-Globins); 0 (gamma-Globins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171029
[Lr] Data última revisão:
171029
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170917
[St] Status:MEDLINE
[do] DOI:10.1101/gad.303461.117


  2 / 2919 MEDLINE  
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[PMID]:28784691
[Au] Autor:Lam WKJ; Gai W; Sun K; Wong RSM; Chan RWY; Jiang P; Chan NPH; Hui WWI; Chan AWH; Szeto CC; Ng SC; Law MF; Chan KCA; Chiu RWK; Lo YMD
[Ad] Endereço:Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
[Ti] Título:DNA of Erythroid Origin Is Present in Human Plasma and Informs the Types of Anemia.
[So] Source:Clin Chem;63(10):1614-1623, 2017 Oct.
[Is] ISSN:1530-8561
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: There is much interest in the tissue of origin of circulating DNA in plasma. Data generated using DNA methylation markers have suggested that hematopoietic cells of white cell lineages are important contributors to the circulating DNA pool. However, it is not known whether cells of the erythroid lineage would also release DNA into the plasma. METHODS: Using high-resolution methylation profiles of erythroblasts and other tissue types, 3 genomic loci were found to be hypomethylated in erythroblasts but hypermethylated in other cell types. We developed digital PCR assays for measuring erythroid DNA using the differentially methylated region for each locus. RESULTS: Based on the methylation marker in the ferrochelatase gene, erythroid DNA represented a median of 30.1% of the plasma DNA of healthy subjects. In subjects with anemia of different etiologies, quantitative analysis of circulating erythroid DNA could reflect the erythropoietic activity in the bone marrow. For patients with reduced erythropoietic activity, as exemplified by aplastic anemia, the percentage of circulating erythroid DNA was decreased. For patients with increased but ineffective erythropoiesis, as exemplified by ß-thalassemia major, the percentage was increased. In addition, the plasma concentration of erythroid DNA was found to correlate with treatment response in aplastic anemia and iron deficiency anemia. Plasma DNA analysis using digital PCR assays targeting the other 2 differentially methylated regions showed similar findings. CONCLUSIONS: Erythroid DNA is a hitherto unrecognized major component of the circulating DNA pool and is a noninvasive biomarker for differential diagnosis and monitoring of anemia.
[Mh] Termos MeSH primário: Anemia/sangue
Anemia/genética
Metilação de DNA
DNA/sangue
DNA/genética
Eritroblastos/patologia
[Mh] Termos MeSH secundário: Anemia/diagnóstico
Anemia/patologia
Anemia Aplástica/sangue
Anemia Aplástica/diagnóstico
Anemia Aplástica/genética
Anemia Aplástica/patologia
Anemia Ferropriva/sangue
Anemia Ferropriva/diagnóstico
Anemia Ferropriva/genética
Anemia Ferropriva/patologia
Diagnóstico Diferencial
Eritroblastos/metabolismo
Eritropoese
Ferroquelatase/genética
Seres Humanos
Síndromes Mielodisplásicas/sangue
Síndromes Mielodisplásicas/diagnóstico
Síndromes Mielodisplásicas/genética
Síndromes Mielodisplásicas/patologia
Talassemia beta/sangue
Talassemia beta/diagnóstico
Talassemia beta/genética
Talassemia beta/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9007-49-2 (DNA); EC 4.99.1.1 (Ferrochelatase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1373/clinchem.2017.272401


  3 / 2919 MEDLINE  
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[PMID]:28776729
[Au] Autor:Dai Y; Chen T; Ijaz H; Cho EH; Steinberg MH
[Ad] Endereço:Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, 02118.
[Ti] Título:SIRT1 activates the expression of fetal hemoglobin genes.
[So] Source:Am J Hematol;92(11):1177-1186, 2017 Nov.
[Is] ISSN:1096-8652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:High fetal hemoglobin (HbF, α γ ) levels ameliorate the clinical manifestations of sickle cell disease and ß thalassemia. The mechanisms that repress HbF expression and silence γ-globin genes in adults are incompletely characterized and only a single HbF inducer, hydroxyurea, is approved for treatment, and only in patients with sickle cell disease. We identified SIRT1, a protein deacetylase, as a new inducer of γ-globin. SIRT1 knockdown decreased, while SIRT1 ectopic expression upregulated γ-globin gene (HBG) expression in primary human erythroid cells and in K562 cells. The small molecule SIRT1 activators SRT2104 and SRT1720 enhanced HBG expression in cord blood human erythroblasts and reactivated silenced HBG in adult human erythroblasts. Furthermore, SIRT1 binds in the ß-globin gene cluster locus control region (LCR) and HBG promoters, promotes the looping of the LCR to HBG promoter, and increases the binding of RNA polymerase II and H4K16Ac in the HBG promoter. SIRT1 suppressed the expression of the HBG suppressors BCL11A, KLF1, HDAC1 and HDAC2. Lastly, SIRT1 did not change the proliferation of human erythroid progenitor cells or the expression of differentiation marker CD235a. These data suggest that SIRT1 activates HBG expression through facilitating LCR looping to the HBG promoter, inhibiting the expression of transcriptional suppressors of HBG, and indirectly increasing histone acetylation in the HBG promoter. SIRT1 is a potential therapeutic target for γ-globin gene induction, and small molecule SIRT1 activators might serve as a lead compound for the development of new HbF inducers.
[Mh] Termos MeSH primário: Hemoglobina Fetal/genética
Regulação da Expressão Gênica
Sirtuína 1/metabolismo
Ativação Transcricional
gama-Globinas/genética
[Mh] Termos MeSH secundário: Diferenciação Celular/genética
Proliferação Celular/genética
Expressão Ectópica do Gene
Eritroblastos/metabolismo
Células Precursoras Eritroides/metabolismo
Eritropoese/genética
Hemoglobina Fetal/metabolismo
Técnicas de Silenciamento de Genes
Inativação Gênica
Seres Humanos
Células K562
Região de Controle de Locus Gênico
Especificidade de Órgãos/genética
Regiões Promotoras Genéticas
Ligação Proteica
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Sirtuína 1/genética
gama-Globinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (gamma-Globins); 9034-63-3 (Fetal Hemoglobin); EC 3.5.1.- (Sirtuin 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170805
[St] Status:MEDLINE
[do] DOI:10.1002/ajh.24879


  4 / 2919 MEDLINE  
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[PMID]:28729432
[Au] Autor:Nowak RB; Papoin J; Gokhin DS; Casu C; Rivella S; Lipton JM; Blanc L; Fowler VM
[Ad] Endereço:Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA.
[Ti] Título:Tropomodulin 1 controls erythroblast enucleation via regulation of F-actin in the enucleosome.
[So] Source:Blood;130(9):1144-1155, 2017 Aug 31.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Biogenesis of mammalian red blood cells requires nuclear expulsion by orthochromatic erythoblasts late in terminal differentiation (enucleation), but the mechanism is largely unexplained. Here, we employed high-resolution confocal microscopy to analyze nuclear morphology and F-actin rearrangements during the initiation, progression, and completion of mouse and human erythroblast enucleation in vivo. Mouse erythroblast nuclei acquire a dumbbell-shaped morphology during enucleation, whereas human bone marrow erythroblast nuclei unexpectedly retain their spherical morphology. These morphological differences are linked to differential expression of Lamin isoforms, with primary mouse erythroblasts expressing only Lamin B and primary human erythroblasts only Lamin A/C. We did not consistently identify a continuous F-actin ring at the cell surface constriction in mouse erythroblasts, nor at the membrane protein-sorting boundary in human erythroblasts, which do not have a constriction, arguing against a contractile ring-based nuclear expulsion mechanism. However, both mouse and human erythroblasts contain an F-actin structure at the rear of the translocating nucleus, enriched in tropomodulin 1 (Tmod1) and nonmuscle myosin IIB. We investigated Tmod1 function in mouse and human erythroblasts both in vivo and in vitro and found that absence of Tmod1 leads to enucleation defects in mouse fetal liver erythroblasts, and in CD34 hematopoietic stem and progenitor cells, with increased F-actin in the structure at the rear of the nucleus. This novel structure, the "enucleosome," may mediate common cytoskeletal mechanisms underlying erythroblast enucleation, notwithstanding the morphological heterogeneity of enucleation across species.
[Mh] Termos MeSH primário: Actinas/metabolismo
Núcleo Celular/metabolismo
Eritroblastos/metabolismo
Tropomodulina/metabolismo
[Mh] Termos MeSH secundário: Animais
Medula Óssea/metabolismo
Diferenciação Celular
Forma do Núcleo Celular
Polaridade Celular
Feto/metabolismo
Técnicas de Silenciamento de Genes
Laminas/metabolismo
Fígado/embriologia
Camundongos Endogâmicos C57BL
Miosina não Muscular Tipo IIB/metabolismo
Isoformas de Proteínas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actins); 0 (Lamins); 0 (Protein Isoforms); 0 (Tropomodulin); EC 3.6.1.- (Nonmuscle Myosin Type IIB)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-05-787051


  5 / 2919 MEDLINE  
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[PMID]:28714864
[Au] Autor:Lessard S; Gatof ES; Beaudoin M; Schupp PG; Sher F; Ali A; Prehar S; Kurita R; Nakamura Y; Baena E; Ledoux J; Oceandy D; Bauer DE; Lettre G
[Ad] Endereço:Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada.
[Ti] Título:An erythroid-specific ATP2B4 enhancer mediates red blood cell hydration and malaria susceptibility.
[So] Source:J Clin Invest;127(8):3065-3074, 2017 Aug 01.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The lack of mechanistic explanations for many genotype-phenotype associations identified by GWAS precludes thorough assessment of their impact on human health. Here, we conducted an expression quantitative trait locus (eQTL) mapping analysis in erythroblasts and found erythroid-specific eQTLs for ATP2B4, the main calcium ATPase of red blood cells (rbc). The same SNPs were previously associated with mean corpuscular hemoglobin concentration (MCHC) and susceptibility to severe malaria infection. We showed that Atp2b4-/- mice demonstrate increased MCHC, confirming ATP2B4 as the causal gene at this GWAS locus. Using CRISPR-Cas9, we fine mapped the genetic signal to an erythroid-specific enhancer of ATP2B4. Erythroid cells with a deletion of the ATP2B4 enhancer had abnormally high intracellular calcium levels. These results illustrate the power of combined transcriptomic, epigenomic, and genome-editing approaches in characterizing noncoding regulatory elements in phenotype-relevant cells. Our study supports ATP2B4 as a potential target for modulating rbc hydration in erythroid disorders and malaria infection.
[Mh] Termos MeSH primário: ATPases Transportadoras de Cálcio/genética
Eritrócitos/citologia
Predisposição Genética para Doença
Malária/genética
ATPases Transportadoras de Cálcio da Membrana Plasmática/genética
[Mh] Termos MeSH secundário: Animais
Sistemas CRISPR-Cas
Cálcio/metabolismo
ATPases Transportadoras de Cálcio/metabolismo
Mapeamento Cromossômico
Elementos Facilitadores Genéticos
Epigenômica
Eritroblastos/metabolismo
Perfilação da Expressão Gênica
Redes Reguladoras de Genes
Estudo de Associação Genômica Ampla
Células HEK293
Seres Humanos
Malária/metabolismo
Masculino
Camundongos
Camundongos Transgênicos
Fenótipo
ATPases Transportadoras de Cálcio da Membrana Plasmática/metabolismo
Polimorfismo de Nucleotídeo Único
Locos de Características Quantitativas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.6.1.8 (ATP2B4 protein, human); EC 3.6.3.8 (Calcium-Transporting ATPases); EC 3.6.3.8 (PMCA4 protein, mouse); EC 3.6.3.8 (Plasma Membrane Calcium-Transporting ATPases); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE


  6 / 2919 MEDLINE  
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[PMID]:28694332
[Au] Autor:Peraki I; Palis J; Mavrothalassitis G
[Ad] Endereço:Medical School, University of Crete, Heraklion, Crete, Greece.
[Ti] Título:The Ets2 Repressor Factor (Erf) Is Required for Effective Primitive and Definitive Hematopoiesis.
[So] Source:Mol Cell Biol;37(19), 2017 Oct 01.
[Is] ISSN:1098-5549
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:is a gene for a ubiquitously expressed Ets DNA-binding domain-containing transcriptional repressor. haploinsufficiency causes craniosynostosis in humans and mice, while its absence in mice leads to failed chorioallantoic fusion and death at embryonic day 10.5 (E10.5). In this study, we show that is required in all three waves of embryonic hematopoiesis. Mice lacking in the embryo proper exhibited severe anemia and died around embryonic day 14.5. epiblast-specific knockout embryos had reduced numbers of circulating blood cells from E9.5 onwards, with the development of severe anemia by E14.5. Elimination of resulted in both reduced and more immature primitive erythroblasts at E9.5 to E10.5. Reduced definitive erythroid colony-forming activity was found in the bloodstream of E10.5 embryos and in the fetal liver at E11.5 to E13.5. Finally, elimination of resulted in impaired repopulation ability, indicating that Erf is necessary for hematopoietic stem cell maintenance or differentiation. We conclude that Erf is required for both primitive and erythromyeloid progenitor waves of hematopoietic stem cell (HSC)-independent hematopoiesis as well as for the normal function of HSCs.
[Mh] Termos MeSH primário: Desenvolvimento Embrionário
Eritroblastos/citologia
Células-Tronco Hematopoéticas/citologia
Proteínas Repressoras/genética
Proteínas Repressoras/metabolismo
[Mh] Termos MeSH secundário: Anemia/genética
Animais
Diferenciação Celular
Linhagem da Célula
Proliferação Celular
Embrião de Mamíferos/citologia
Embrião de Mamíferos/embriologia
Embrião de Mamíferos/metabolismo
Eritroblastos/metabolismo
Técnicas de Inativação de Genes
Hematopoese
Células-Tronco Hematopoéticas/metabolismo
Seres Humanos
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Erf protein, mouse); 0 (Repressor Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170712
[St] Status:MEDLINE


  7 / 2919 MEDLINE  
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[PMID]:28570892
[Au] Autor:Montalvão MF; de Souza JM; Guimarães ATB; de Menezes IPP; Castro ALDS; Rodrigues ASL; Malafaia G
[Ad] Endereço:Laboratório de Pesquisas Biológicas, Instituto Federal Goiano - Campus Urutaí, GO, Brazil.
[Ti] Título:The genotoxicity and cytotoxicity of tannery effluent in bullfrog (Lithobates catesbeianus).
[So] Source:Chemosphere;183:491-502, 2017 Sep.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Some of the most polluting activities occur in bovine skin processing. Tannery generates effluents containing high concentrations of heavy metals and organic compounds. The phases composing the leather production process generate a large volume of tannery effluents that are often discarded in aquatic environments without any previous treatment. However, the effect these xenobiotics have on adult representatives belonging to the class Amphibia remains unknown. Thus, the aim of the present study is to assess the geno- and cytotoxic effects of tannery effluent on adult male bullfrogs (Lithobates castesbeianus) exposed to it. Accordingly, the animals were divided into the following groups: negative control (tannery effluent-free water), positive control (cyclophosphamide), and effluent (water added with 5% tannery effluent). The animals were euthanized for blood collection, and erythrocyte analyses were conducted after 35 and 90 days of exposure. The micronuclei (MN) frequency and the frequency of other nuclear abnormalities in each of the animals in the experimental groups were assessed in 2000 erythrocytes. According to the present results, the exposure to tannery effluents increased MN frequency as well as other nuclear abnormalities (i.e., lobed nuclei, binucleated cell, kidney-shaped nuclei, notched nuclei, and apoptotic cell) in the erythrocytes of animals in the effluent group and in the positive control group after 35 and 90 exposure days. Thus, the current study corroborated the hypothesis that the tannery effluent has aneugenic and clastogenic potential in adult male bullfrogs (L. castesbeianus). The present study is the first to report such effect.
[Mh] Termos MeSH primário: Eritrócitos/efeitos dos fármacos
Metais Pesados/toxicidade
Micronúcleos com Defeito Cromossômico/induzido quimicamente
Mutagênicos/toxicidade
Curtume
Poluentes Químicos da Água/toxicidade
[Mh] Termos MeSH secundário: Animais
Dano ao DNA
Relação Dose-Resposta a Droga
Eritroblastos/química
Eritroblastos/efeitos dos fármacos
Eritroblastos/patologia
Eritrócitos/química
Eritrócitos/patologia
Eritrócitos Anormais/química
Eritrócitos Anormais/efeitos dos fármacos
Eritrócitos Anormais/patologia
Resíduos Industriais/análise
Masculino
Metais Pesados/análise
Testes para Micronúcleos
Estrutura Molecular
Mutagênicos/análise
Rana catesbeiana
Fatores de Tempo
Poluentes Químicos da Água/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Industrial Waste); 0 (Metals, Heavy); 0 (Mutagens); 0 (Water Pollutants, Chemical)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE


  8 / 2919 MEDLINE  
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[PMID]:28553950
[Au] Autor:Duchene J; Novitzky-Basso I; Thiriot A; Casanova-Acebes M; Bianchini M; Etheridge SL; Hub E; Nitz K; Artinger K; Eller K; Caamaño J; Rülicke T; Moss P; Megens RTA; von Andrian UH; Hidalgo A; Weber C; Rot A
[Ad] Endereço:Institute for Cardiovascular Prevention, Ludwig-Maximilians University (LMU), Munich, Germany.
[Ti] Título:Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis.
[So] Source:Nat Immunol;18(7):753-761, 2017 Jul.
[Is] ISSN:1529-2916
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Healthy individuals of African ancestry have neutropenia that has been linked with the variant rs2814778(G) of the gene encoding atypical chemokine receptor 1 (ACKR1). This polymorphism selectively abolishes the expression of ACKR1 in erythroid cells, causing a Duffy-negative phenotype. Here we describe an unexpected fundamental role for ACKR1 in hematopoiesis and provide the mechanism that links its absence with neutropenia. Nucleated erythroid cells had high expression of ACKR1, which facilitated their direct contact with hematopoietic stem cells. The absence of erythroid ACKR1 altered mouse hematopoiesis including stem and progenitor cells, which ultimately gave rise to phenotypically distinct neutrophils that readily left the circulation, causing neutropenia. Individuals with a Duffy-negative phenotype developed a distinct profile of neutrophil effector molecules that closely reflected the one observed in the ACKR1-deficient mice. Thus, alternative physiological patterns of hematopoiesis and bone marrow cell outputs depend on the expression of ACKR1 in the erythroid lineage, findings with major implications for the selection advantages that have resulted in the paramount fixation of the ACKR1 rs2814778(G) polymorphism in Africa.
[Mh] Termos MeSH primário: Sistema do Grupo Sanguíneo Duffy/metabolismo
Eritroblastos/metabolismo
Hematopoese/genética
Células-Tronco Hematopoéticas/metabolismo
Neutropenia/genética
Neutrófilos/metabolismo
Receptores de Superfície Celular/metabolismo
[Mh] Termos MeSH secundário: Grupo com Ancestrais do Continente Africano/genética
Animais
Medula Óssea/patologia
Células da Medula Óssea/metabolismo
Proliferação Celular
Sistema do Grupo Sanguíneo Duffy/genética
Citometria de Fluxo
Imunofluorescência
Células-Tronco Hematopoéticas/citologia
Seres Humanos
Camundongos
Microscopia Confocal
Neutrófilos/citologia
Receptores de Superfície Celular/genética
Receptores de Quimiocinas/genética
Receptores de Quimiocinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DARC protein, human); 0 (Dfy protein, mouse); 0 (Duffy Blood-Group System); 0 (Receptors, Cell Surface); 0 (Receptors, Chemokine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE
[do] DOI:10.1038/ni.3763


  9 / 2919 MEDLINE  
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[PMID]:28381471
[Au] Autor:Zhang L; Jambusaria A; Hong Z; Marsboom G; Toth PT; Herbert BS; Malik AB; Rehman J
[Ad] Endereço:From Department of Pharmacology (L.Z., A.J., Z.H., G.M., P.T.T., A.B.M., J.R.), Department of Medicine, Division of Cardiology (J.R.), The University of Illinois College of Medicine, Chicago; and Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis (B.-S.
[Ti] Título:SOX17 Regulates Conversion of Human Fibroblasts Into Endothelial Cells and Erythroblasts by Dedifferentiation Into CD34 Progenitor Cells.
[So] Source:Circulation;135(25):2505-2523, 2017 Jun 20.
[Is] ISSN:1524-4539
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The mechanisms underlying the dedifferentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is not known whether fibroblast dedifferentiation recapitulates the generation of multipotent progenitors during embryonic development, which give rise to endothelial and hematopoietic cell lineages. Here we established the role of the developmental transcription factor SOX17 in regulating the bilineage conversion of fibroblasts by the generation of intermediate progenitors. METHODS: CD34 progenitors were generated after the dedifferentiation of human adult dermal fibroblasts by overexpression of pluripotency transcription factors. Sorted CD34 cells were transdifferentiated into induced endothelial cells and induced erythroblasts using lineage-specific growth factors. The therapeutic potential of the generated cells was assessed in an experimental model of myocardial infarction. RESULTS: Induced endothelial cells expressed specific endothelial cell surface markers and also exhibited the capacity for cell proliferation and neovascularization. Induced erythroblasts expressed erythroid surface markers and formed erythroid colonies. Endothelial lineage conversion was dependent on the upregulation of the developmental transcription factor SOX17, whereas suppression of SOX17 instead directed the cells toward an erythroid fate. Implantation of these human bipotential CD34 progenitors into nonobese diabetic/severe combined immunodeficiency (NOD-SCID) mice resulted in the formation of microvessels derived from human fibroblasts perfused with mouse and human erythrocytes. Endothelial cells generated from human fibroblasts also showed upregulation of telomerase. Cell implantation markedly improved vascularity and cardiac function after myocardial infarction without any evidence of teratoma formation. CONCLUSIONS: Dedifferentiation of fibroblasts to intermediate CD34 progenitors gives rise to endothelial cells and erythroblasts in a SOX17-dependent manner. These findings identify the intermediate CD34 progenitor state as a critical bifurcation point, which can be tuned to generate functional blood vessels or erythrocytes and salvage ischemic tissue.
[Mh] Termos MeSH primário: Antígenos CD34/fisiologia
Desdiferenciação Celular/fisiologia
Células Endoteliais/fisiologia
Eritroblastos/fisiologia
Fibroblastos/fisiologia
Fatores de Transcrição SOXF/fisiologia
Células-Tronco/fisiologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Seres Humanos
Recém-Nascido
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD34); 0 (SOX17 protein, human); 0 (SOXF Transcription Factors)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCULATIONAHA.116.025722


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[PMID]:28370131
[Au] Autor:Cooling L; Roxbury K; Hoffmann S; DeBusscher J; Kota U; Goldstein S; Davenport R
[Ad] Endereço:Department of Pathology, University of Michigan, Ann Arbor, Michigan.
[Ti] Título:Use of allogeneic apheresis stem cell products as an interlaboratory proficiency challenge.
[So] Source:Transfusion;57(6):1543-1554, 2017 Jun.
[Is] ISSN:1537-2995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: AABB Standards requires that laboratories participate in a proficiency test (PT) program for critical analytes. Institutions can purchase commercial PT materials; however, PT can also be performed through interlaboratory exchange. We investigated the utility of allogeneic hematopoietic progenitor cell apheresis (HPC-A) products as an interlaboratory PT challenge for total nucleated cell count (TNC) and CD34 assessment. STUDY DESIGN AND METHODS: Three-year retrospective and comparative review of unrelated allogeneic HPC-A products received by the University of Michigan between January 2011 and December 2013. Internal TNC and CD34 count were compared to the external collecting facility by paired t test and linear regression. The absolute and percent difference between external and internal counts and 95% limits of agreeability (95% LA) were determined. Results were analyzed relative to donor center location (international, domestic), time zone (domestic), and calendar year. RESULTS: There was a strong correlation between internal and external TNC, regardless of donor center location or year. For CD34, there was a good correlation between centers (R = 0.88-0.91; slope = 0.95-0.98x) with a median difference of -1% (95% LA, -50%, +47%). This was considerably better than commercial PT challenges, which showed a persistent negative bias for absolute CD34 and CD3 counts. CONCLUSION: Allogeneic HPC-A products represent an interlaboratory PT exchange for all critical analytes, including TNC and CD34 count, cell viability, and sterility. Allogeneic HPC-A products, which are fresh and transported under validated conditions, are less subject to preanalytical variables that may impact commercial PT samples such as aliquoting and sample homogeneity, commercial additives, and sample stability during manufacturing and transport.
[Mh] Termos MeSH primário: Remoção de Componentes Sanguíneos
Células-Tronco/citologia
[Mh] Termos MeSH secundário: Adulto
Aloenxertos
Antígenos CD34/imunologia
Sobrevivência Celular/fisiologia
Eritroblastos/metabolismo
Feminino
Células-Tronco Hematopoéticas/citologia
Células-Tronco Hematopoéticas/metabolismo
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
Células-Tronco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD34)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE
[do] DOI:10.1111/trf.14107



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