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Pesquisa : G04.172 [Categoria DeCS]
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  1 / 20480 MEDLINE  
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[PMID]:29314175
[Au] Autor:Cohn M
[Ad] Endereço:Conceptual Immunology Group, The Salk Institute, La Jolla, CA, USA.
[Ti] Título:Somatic diversification of the B cell repertoire requires two cell subsets.
[So] Source:Scand J Immunol;87(3), 2018 Mar.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Evolution found itself in a Catch-22 situation when selecting for the somatically derived paratopic repertoire of the humoral immune system. The B cell BCR repertoire can only be somatically diversified from a substrate of paratopes that is encoded in the germline. In order for the cells expressing that substrate to also be a target of germline selection, their BCRs must, independently, be of selective value by being expressed in a functionally important way in each individual. A somatically derived repertoire scrambles this substrate so that its specificities are lost, making it unselectable in the germline. Consequently, evolution faced an incompatibility. Here, we explore what it takes to resolve it.
[Mh] Termos MeSH primário: Subpopulações de Linfócitos B/citologia
Sítios de Ligação de Anticorpos/imunologia
Diferenciação Celular/imunologia
Região Variável de Imunoglobulina/imunologia
Anticorpos de Domínio Único/imunologia
[Mh] Termos MeSH secundário: Anticorpos/imunologia
Subpopulações de Linfócitos B/imunologia
Linhagem da Célula/imunologia
Genes de Imunoglobulinas
Seres Humanos
Imunidade Humoral/imunologia
Região Variável de Imunoglobulina/genética
Anticorpos de Domínio Único/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (Immunoglobulin Variable Region); 0 (Single-Domain Antibodies)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12640


  2 / 20480 MEDLINE  
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[PMID]:29382818
[Au] Autor:Sánchez-Iranzo H; Galardi-Castilla M; Minguillón C; Sanz-Morejón A; González-Rosa JM; Felker A; Ernst A; Guzmán-Martínez G; Mosimann C; Mercader N
[Ad] Endereço:Development of the Epicardium and Its Role during Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029, Madrid, Spain.
[Ti] Título:Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration.
[So] Source:Nat Commun;9(1):428, 2018 01 30.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:During development, mesodermal progenitors from the first heart field (FHF) form a primitive cardiac tube, to which progenitors from the second heart field (SHF) are added. The contribution of FHF and SHF progenitors to the adult zebrafish heart has not been studied to date. Here we find, using genetic tbx5a lineage tracing tools, that the ventricular myocardium in the adult zebrafish is mainly derived from tbx5a cells, with a small contribution from tbx5a SHF progenitors. Notably, ablation of ventricular tbx5a -derived cardiomyocytes in the embryo is compensated by expansion of SHF-derived cells. In the adult, tbx5a expression is restricted to the trabeculae and excluded from the outer cortical layer. tbx5a-lineage tracing revealed that trabecular cardiomyocytes can switch their fate and differentiate into cortical myocardium during adult heart regeneration. We conclude that a high degree of cardiomyocyte cell fate plasticity contributes to efficient regeneration.
[Mh] Termos MeSH primário: Ventrículos do Coração/citologia
Miocárdio/citologia
Miócitos Cardíacos/citologia
Regeneração/genética
Proteínas com Domínio T-Box/genética
Peixe-Zebra/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Diferenciação Celular
Linhagem da Célula/genética
Rastreamento de Células
Embrião não Mamífero
Regulação da Expressão Gênica no Desenvolvimento
Genes Reporter
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Ventrículos do Coração/crescimento & desenvolvimento
Ventrículos do Coração/metabolismo
Proteínas Luminescentes/genética
Proteínas Luminescentes/metabolismo
Miocárdio/metabolismo
Miócitos Cardíacos/metabolismo
Cadeias Leves de Miosina/genética
Cadeias Leves de Miosina/metabolismo
Organogênese/genética
Células-Tronco/citologia
Células-Tronco/metabolismo
Proteínas com Domínio T-Box/deficiência
Peixe-Zebra/crescimento & desenvolvimento
Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Luminescent Proteins); 0 (Myosin Light Chains); 0 (T-Box Domain Proteins); 0 (T-box transcription factor 5); 0 (red fluorescent protein); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02650-6


  3 / 20480 MEDLINE  
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[PMID]:29207259
[Au] Autor:Chen X; Wang R; Liu X; Wu Y; Zhou T; Yang Y; Perez A; Chen YC; Hu L; Chadarevian JP; Assadieskandar A; Zhang C; Ying QL
[Ad] Endereço:Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
[Ti] Título:A Chemical-Genetic Approach Reveals the Distinct Roles of GSK3α and GSK3ß in Regulating Embryonic Stem Cell Fate.
[So] Source:Dev Cell;43(5):563-576.e4, 2017 Dec 04.
[Is] ISSN:1878-1551
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycogen synthase kinase 3 (GSK3) plays a central role in diverse cellular processes. GSK3 has two mammalian isozymes, GSK3α and GSK3ß, whose functions remain ill-defined because of a lack of inhibitors that can distinguish between the two highly homologous isozymes. Here, we show that GSK3α and GSK3ß can be selectively inhibited in mouse embryonic stem cells (ESCs) using a chemical-genetic approach. Selective inhibition of GSK3ß is sufficient to maintain mouse ESC self-renewal, whereas GSK3α inhibition promotes mouse ESC differentiation toward neural lineages. Genome-wide transcriptional analysis reveals that GSK3α and GSK3ß have distinct sets of downstream targets. Furthermore, selective inhibition of individual GSK3 isozymes yields distinct phenotypes from gene deletion, highlighting the power of the chemical-genetic approach in dissecting kinase catalytic functions from the protein's scaffolding functions. Our study opens new avenues for defining GSK3 isozyme-specific functions in various cellular processes.
[Mh] Termos MeSH primário: Diferenciação Celular/fisiologia
Linhagem da Célula
Glicogênio Sintase Quinase 3 beta/genética
Quinase 3 da Glicogênio Sintase/genética
Células-Tronco Embrionárias Murinas/citologia
[Mh] Termos MeSH secundário: Animais
Estudo de Associação Genômica Ampla/métodos
Camundongos
Camundongos Knockout
Fosforilação
Transdução de Sinais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta); EC 2.7.11.26 (Glycogen Synthase Kinase 3); EC 2.7.11.26 (glycogen synthase kinase 3 alpha)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE


  4 / 20480 MEDLINE  
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[PMID]:29311541
[Au] Autor:Stremmel C; Schuchert R; Wagner F; Thaler R; Weinberger T; Pick R; Mass E; Ishikawa-Ankerhold HC; Margraf A; Hutter S; Vagnozzi R; Klapproth S; Frampton J; Yona S; Scheiermann C; Molkentin JD; Jeschke U; Moser M; Sperandio M; Massberg S; Geissmann F; Schulz C
[Ad] Endereço:Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Marchioninistrasse 15, 81377, Munich, Germany.
[Ti] Título:Yolk sac macrophage progenitors traffic to the embryo during defined stages of development.
[So] Source:Nat Commun;9(1):75, 2018 01 08.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Tissue macrophages in many adult organs originate from yolk sac (YS) progenitors, which invade the developing embryo and persist by means of local self-renewal. However, the route and characteristics of YS macrophage trafficking during embryogenesis are incompletely understood. Here we show the early migration dynamics of YS-derived macrophage progenitors in vivo using fate mapping and intravital microscopy. From embryonic day 8.5 (E8.5) CX CR1+ pre-macrophages are present in the mouse YS where they rapidly proliferate and gain access to the bloodstream to migrate towards the embryo. Trafficking of pre-macrophages and their progenitors from the YS to tissues peaks around E10.5, dramatically decreases towards E12.5 and is no longer evident from E14.5 onwards. Thus, YS progenitors use the vascular system during a restricted time window of embryogenesis to invade the growing fetus. These findings close an important gap in our understanding of the development of the innate immune system.
[Mh] Termos MeSH primário: Movimento Celular
Células-Tronco Embrionárias/citologia
Macrófagos/citologia
Saco Vitelino/citologia
[Mh] Termos MeSH secundário: Animais
Circulação Sanguínea
Linhagem da Célula
Proliferação Celular
Embrião de Mamíferos/irrigação sanguínea
Embrião de Mamíferos/citologia
Embrião de Mamíferos/embriologia
Células-Tronco Hematopoéticas/citologia
Camundongos Endogâmicos C57BL
Camundongos Knockout
Camundongos Transgênicos
Microscopia Confocal
Fatores de Tempo
Saco Vitelino/embriologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02492-2


  5 / 20480 MEDLINE  
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[PMID]:28460641
[Au] Autor:Bernardi M; Agostini F; Chieregato K; Amati E; Durante C; Rassu M; Ruggeri M; Sella S; Lombardi E; Mazzucato M; Astori G
[Ad] Endereço:Advanced Cellular Therapy Laboratory, Hematology Unit, Vicenza Hospital, Vicenza, Italy.
[Ti] Título:The production method affects the efficacy of platelet derivatives to expand mesenchymal stromal cells in vitro.
[So] Source:J Transl Med;15(1):90, 2017 May 01.
[Is] ISSN:1479-5876
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The use of fetal bovine serum (FBS) as a media supplement for the ex vivo expansion of bone-marrow derived mesenchymal stromal cells (BM-MSC) has been discouraged by regulatory agencies, due to the risk of transmitting zoonoses and to elicit immune reactions in the host once transplanted. Platelet derivatives are valid FBS substitutes due to their content of growth factors that can be released disrupting the platelets by physical methods or physiological stimuli. We compared platelet derivatives produced by freezing/thawing (platelet lysates, PL) or after CaCl activation (platelet releasate surnatant rich in growth factors, PR-SRGF) for their content in growth factors and their ability to support the ex vivo expansion of BM-MSC. METHODS: The cytokine content in the two platelet derivatives was evaluated. BM-MSC were expanded in complete medium containing 10, 7.5 and 5% PL or PR-SRGF and the cell phenotype, clonogenic capacity, immunomodulation properties and tri-lineage differentiation potential of the expanded cells in both media were investigated. RESULTS: The concentration of PDGF-AB, PDGF-AA, PDGF-BB in PR-SRGF resulted to be respectively 5.7×, 1.7× and 2.3× higher compared to PL. PR-SRGF promoted a higher BM-MSC proliferation rate compared to PL not altering BM-MSC phenotype. Colony forming efficiency of BM-MSC expanded in PR-SRGF showed a frequency of colonies significantly higher than cells expanded in PL. BM-MSC expanded in PL or PR-SRGF maintained their immunomodulatory properties against activated lymphocytes even if BM-MSC expanded in FBS performed significantly better. CONCLUSIONS: The method used to release platelet factors significantly affects the enrichment in growth factors and overall product performance. The standardization of the production process of platelet derivatives and the definition of their release criteria requires further investigation.
[Mh] Termos MeSH primário: Plaquetas/metabolismo
Técnicas de Cultura de Células/métodos
Células Mesenquimais Estromais/citologia
[Mh] Termos MeSH secundário: Diferenciação Celular
Linhagem da Célula
Proliferação Celular
Ensaio de Unidades Formadoras de Colônias
Seres Humanos
Imunomodulação
Imunofenotipagem
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intercellular Signaling Peptides and Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1186/s12967-017-1185-9


  6 / 20480 MEDLINE  
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[PMID]:28454545
[Au] Autor:Vellutini BC; Martín-Durán JM; Hejnol A
[Ad] Endereço:Sars International Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgate 55, 5006, Bergen, Norway.
[Ti] Título:Cleavage modification did not alter blastomere fates during bryozoan evolution.
[So] Source:BMC Biol;15(1):33, 2017 04 28.
[Is] ISSN:1741-7007
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Stereotypic cleavage patterns play a crucial role in cell fate determination by precisely positioning early embryonic blastomeres. Although misplaced cell divisions can alter blastomere fates and cause embryonic defects, cleavage patterns have been modified several times during animal evolution. However, it remains unclear how evolutionary changes in cleavage impact the specification of blastomere fates. Here, we analyze the transition from spiral cleavage - a stereotypic pattern remarkably conserved in many protostomes - to a biradial cleavage pattern, which occurred during the evolution of bryozoans. RESULTS: Using 3D-live imaging time-lapse microscopy (4D-microscopy), we characterize the cell lineage, MAPK signaling, and the expression of 16 developmental genes in the bryozoan Membranipora membranacea. We found that the molecular identity and the fates of early bryozoan blastomeres are similar to the putative homologous blastomeres in spiral-cleaving embryos. CONCLUSIONS: Our work suggests that bryozoans have retained traits of spiral development, such as the early embryonic fate map, despite the evolution of a novel cleavage geometry. These findings provide additional support that stereotypic cleavage patterns can be modified during evolution without major changes to the molecular identity and fate of embryonic blastomeres.
[Mh] Termos MeSH primário: Evolução Biológica
Blastômeros/fisiologia
Briozoários/embriologia
Diferenciação Celular
Linhagem da Célula
[Mh] Termos MeSH secundário: Animais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1186/s12915-017-0371-9


  7 / 20480 MEDLINE  
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[PMID]:28455282
[Au] Autor:Sim X; Jarocha D; Hayes V; Hanby HA; Marks MS; Camire RM; French DL; Poncz M; Gadue P
[Ad] Endereço:Department of Cell and Molecular Biology, University of Pennsylvania School of Medicine, Philadelphia, PA.
[Ti] Título:Identifying and enriching platelet-producing human stem cell-derived megakaryocytes using factor V uptake.
[So] Source:Blood;130(2):192-204, 2017 07 13.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Stem cell-derived platelets have the potential to replace donor platelets for transfusion. Defining the platelet-producing megakaryocytes (MKs) within the heterogeneous MK culture may help to optimize the in vitro generation of platelets. Using 2 human stem cell models of megakaryopoiesis, we identified novel MK populations corresponding to distinct maturation stages. An immature, low granular (LG) MK pool (defined by side scatter on flow cytometry) gives rise to a mature high granular (HG) pool, which then becomes damaged by apoptosis and glycoprotein Ib α chain (CD42b) shedding. We define an undamaged HG/CD42b MK subpopulation, which endocytoses fluorescently labeled coagulation factor V (FV) from the media into α-granules and releases functional FV CD42b human platelet-like particles in vitro and when infused into immunodeficient mice. Importantly, these FV particles have the same size distribution as infused human donor platelets and are preferentially incorporated into clots after laser injury. Using drugs to protect HG MKs from apoptosis and CD42b shedding, we also demonstrate that apoptosis precedes CD42b shedding and that apoptosis inhibition enriches the FV HG/CD42b MKs, leading to increased platelet yield in vivo, but not in vitro. These studies identify a transition between distinct MK populations in vitro, including one that is primed for platelet release. Technologies to optimize and select these platelet-ready MKs may be important to efficiently generate functional platelets from in vitro-grown MKs.
[Mh] Termos MeSH primário: Plaquetas/citologia
Células da Medula Óssea/imunologia
Fator V/genética
Células Progenitoras de Megacariócitos/citologia
Megacariócitos/citologia
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Arteríolas/efeitos dos fármacos
Arteríolas/imunologia
Arteríolas/lesões
Biomarcadores/sangue
Plaquetas/imunologia
Células da Medula Óssea/citologia
Células da Medula Óssea/efeitos dos fármacos
Diferenciação Celular
Linhagem da Célula/imunologia
Endocitose
Fator V/imunologia
Fator V/farmacologia
Citometria de Fluxo
Expressão Gênica
Seres Humanos
Imunofenotipagem
Lasers
Células Progenitoras de Megacariócitos/imunologia
Megacariócitos/imunologia
Camundongos
Camundongos SCID
Complexo Glicoproteico GPIb-IX de Plaquetas/genética
Complexo Glicoproteico GPIb-IX de Plaquetas/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Biomarkers); 0 (Platelet Glycoprotein GPIb-IX Complex); 9001-24-5 (Factor V)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-01-761049


  8 / 20480 MEDLINE  
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[PMID]:28463231
[Au] Autor:Gaskill CF; Carrier EJ; Kropski JA; Bloodworth NC; Menon S; Foronjy RF; Taketo MM; Hong CC; Austin ED; West JD; Means AL; Loyd JE; Merryman WD; Hemnes AR; De Langhe S; Blackwell TS; Klemm DJ; Majka SM
[Ad] Endereço:Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine or Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee USA.
[Ti] Título:Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction.
[So] Source:J Clin Invest;127(6):2262-2276, 2017 Jun 01.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pulmonary vascular disease is characterized by remodeling and loss of microvessels and is typically attributed to pathological responses in vascular endothelium or abnormal smooth muscle cell phenotypes. We have challenged this understanding by defining an adult pulmonary mesenchymal progenitor cell (MPC) that regulates both microvascular function and angiogenesis. The current understanding of adult MPCs and their roles in homeostasis versus disease has been limited by a lack of genetic markers with which to lineage label multipotent mesenchyme and trace the differentiation of these MPCs into vascular lineages. Here, we have shown that lineage-labeled lung MPCs expressing the ATP-binding cassette protein ABCG2 (ABCG2+) are pericyte progenitors that participate in microvascular homeostasis as well as adaptive angiogenesis. Activation of Wnt/ß-catenin signaling, either autonomously or downstream of decreased BMP receptor signaling, enhanced ABCG2+ MPC proliferation but suppressed MPC differentiation into a functional pericyte lineage. Thus, enhanced Wnt/ß-catenin signaling in ABCG2+ MPCs drives a phenotype of persistent microvascular dysfunction, abnormal angiogenesis, and subsequent exacerbation of bleomycin-induced fibrosis. ABCG2+ MPCs may, therefore, account in part for the aberrant microvessel function and remodeling that are associated with chronic lung diseases.
[Mh] Termos MeSH primário: Células Mesenquimais Estromais/fisiologia
Microvasos/fisiopatologia
[Mh] Termos MeSH secundário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Animais
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo
Diferenciação Celular
Linhagem da Célula
Células Cultivadas
Seres Humanos
Pulmão/irrigação sanguínea
Camundongos Transgênicos
Microvasos/patologia
Neovascularização Patológica/metabolismo
Pericitos/fisiologia
Estabilidade Proteica
Fibrose Pulmonar/metabolismo
Fibrose Pulmonar/patologia
Vasoconstrição
Via de Sinalização Wnt
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Abcg2 protein, mouse); EC 2.7.11.30 (Bmpr2 protein, mouse); EC 2.7.11.30 (Bone Morphogenetic Protein Receptors, Type II)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  9 / 20480 MEDLINE  
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[PMID]:28450163
[Au] Autor:Ganuza M; Hadland B; Chabot A; Li C; Kang G; Bernstein I; McKinney-Freeman S
[Ad] Endereço:Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN.
[Ti] Título:Murine hemogenic endothelial precursors display heterogeneous hematopoietic potential ex vivo.
[So] Source:Exp Hematol;51:25-35.e6, 2017 07.
[Is] ISSN:1873-2399
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Hematopoietic stem and progenitor cells (HSPCs) sustain life-long hematopoiesis and are first detected in the embryo by transplantation at embryonic day 10.5 (E10.5). HSPCs are mesodermal in origin and ultimately emerge from a subset of arterial endothelium (i.e., hemogenic endothelium [HE]), which is highly concentrated in the aorta-gonad-mesonephros region of the midgestation embryo. Here, we used clonal ex vivo assays, in which endothelial cells isolated from the midgestation aorta and vitelline and umbilical arteries are co-cultured on supportive stroma, to show that only about 0.1%, 1.3%, and 0.29% of E9.5, E10.5, and E11.5 endothelium are functional HE, respectively. We further show high phenotypic and functional variability in the hematopoietic potential of individual hemogenic endothelial precursors. Using unique niche stroma capable of providing the signals necessary for definitive hematopoietic stem cell (dHSC) induction, we demonstrate that this variability in HE includes their potential to support phenotypic dHSCs. These data suggest the presence of a continuum of maturing HE with distinct hematopoietic potential or HE representative of a heterogeneous pool of precursors that give rise to HSPCs with disparate hematopoietic potential.
[Mh] Termos MeSH primário: Linhagem da Célula/fisiologia
Embrião de Mamíferos/embriologia
Células Endoteliais/metabolismo
Hematopoese/fisiologia
Células-Tronco Hematopoéticas/metabolismo
[Mh] Termos MeSH secundário: Animais
Embrião de Mamíferos/citologia
Células Endoteliais/citologia
Células-Tronco Hematopoéticas/citologia
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180224
[Lr] Data última revisão:
180224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


  10 / 20480 MEDLINE  
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[PMID]:29381029
[Au] Autor:Yoo J; Chang Y; Kim H; Baek S; Choi H; Jeong GJ; Shin J; Kim H; Kim BS; Kim J
[Ti] Título:Efficient Direct Lineage Reprogramming of Fibroblasts into Induced Cardiomyocytes Using Nanotopographical Cues.
[So] Source:J Biomed Nanotechnol;13(3):269-79, 2017 Mar.
[Is] ISSN:1550-7033
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Induced cardiomyocytes (iCMs) generated via direct lineage reprogramming offer a novel therapeutic target for the study and treatment of cardiac diseases. However, the efficiency of iCM generation is significantly low for therapeutic applications. Here, we show an efficient direct conversion of somatic fibroblasts into iCMs using nanotopographic cues. Compared with flat substrates, the direct conversion of fibroblasts into iCMs on nanopatterned substrates resulted in a dramatic increase in the reprogramming efficiency and maturation of iCM phenotypes. Additionally, enhanced reprogramming by substrate nanotopography was due to changes in the activation of focal adhesion kinase and specific histone modifications. Taken together, these results suggest that nanotopographic cues can serve as an efficient stimulant for direct lineage reprogramming into iCMs.
[Mh] Termos MeSH primário: Técnicas de Reprogramação Celular/métodos
Fibroblastos/citologia
Fibroblastos/fisiologia
Miócitos Cardíacos/citologia
Miócitos Cardíacos/fisiologia
Nanopartículas/química
Nanopartículas/ultraestrutura
[Mh] Termos MeSH secundário: Animais
Técnicas de Cultura Celular por Lotes/métodos
Adesão Celular/fisiologia
Diferenciação Celular/fisiologia
Linhagem da Célula/fisiologia
Polaridade Celular/fisiologia
Proliferação Celular/fisiologia
Tamanho Celular
Células Cultivadas
Camundongos
Propriedades de Superfície
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE



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