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1.
Chem Asian J ; : e202400316, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38818666

RESUMO

Tricolor electrochromism was realized through the interconversion among the neutral (yellow), dicationic (green), and tetracationic (blue) states, even though only one kind of chromophore is generated upon oxidation. Both dicationic and tetracationic states were isolated as stable salts, and their different colors come from the effective interchromophore interaction only in the tetracationic state but not in the dicationic state. Despite the negligible Coulombic repulsion in the tetracationic state with four cyanine-type chromophores, pentacenebisquinodimethane undergoes stepwise two-stage two-electron oxidation when radical-stabilizing 5-(4-octyloxyphenyl)-2-thienyl groups are attached on the exomethylene bonds. A contribution from the biradical form only in the neutral state but not in the dicationic state is the reason for the observed negative cooperativity during the electrochemical oxidation.

2.
Chemistry ; 30(35): e202400916, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38644537

RESUMO

Upon dibenzo annulation on Thiele's hydrocarbon (tetraphenyl-p-quinodimethane), the quinoid form and the biradical form adopt quite different geometries, and thus are no longer resonance structures. When these two forms can interconvert rapidly due to the small energy barrier (ΔG≠), the equilibrated mixture contains both forms in a ratio that is determined by the energy difference (ΔGo) between the two forms. For a series of tetrakis[5-(4-methoxyphenyl)-2-thienyl]-substituted derivatives, the more stable quinoid form and the metastable biradical form coexist in solution as an equilibrated mixture due to small ΔG≠ (<15 kcal mol-1) and ΔGo (1-4 kcal mol-1), in which the proportion of the two forms can be regulated by temperature. Since the biradical form can undergo easy two-electron (2e) oxidation to the corresponding dications as well as easy 2e-reduction to the dianions, it exhibits very high electrochemical amphotericity. This character with a record-small span for not only the first oxidation and reduction potentials but also the second those, [E1 sum≈E2 sum=E2 ox-E2 red=ca. 1.4 V], is attained through thermally enhanced conversion to the biradical form from the corresponding quinoid form, the latter of which is less amphoteric due to higher Eox and lower Ered values.

3.
PLoS One ; 8(6): e66269, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23824717

RESUMO

p600 is a multifunctional protein implicated in cytoskeletal organization, integrin-mediated survival signaling, calcium-calmodulin signaling and the N-end rule pathway of ubiquitin-proteasome-mediated proteolysis. While push, the Drosophila counterpart of p600, is dispensable for development up to adult stage, the role of p600 has not been studied during mouse development. Here we generated p600 knockout mice to investigate the in vivo functions of p600. Interestingly, we found that homozygous deletion of p600 results in lethality between embryonic days 11.5 and 13.5 with severe defects in both embryo and placenta. Since p600 is required for placental development, we performed conditional disruption of p600, which deletes selectively p600 in the embryo but not in the placenta. The conditional mutant embryos survive longer than knockout embryos but ultimately die before embryonic day 14.5. The mutant embryos display severe cardiac problems characterized by ventricular septal defects and thin ventricular walls. These anomalies are associated with reduced activation of FAK and decreased expression of MEF2, which is regulated by FAK and plays a crucial role in cardiac development. Moreover, we observed pleiotropic defects in the liver and brain. In sum, our study sheds light on the essential roles of p600 in fetal development.


Assuntos
Potenciais Evocados , Desenvolvimento Fetal/fisiologia , Animais , Potenciais Evocados/genética , Deleção de Genes , Camundongos , Camundongos Knockout
4.
Blood ; 114(24): 5034-43, 2009 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-19808698

RESUMO

Myeloid cell leukemia-1 (MCL-1) is an essential survival factor for hematopoiesis. In humans, hematopoietic stem cells (HSCs) express MCL-1 at the highest level in response to FMS-like tyrosine kinase-3 (FLT3) signaling. We here show that this FLT3-dependent stem cell maintenance system also plays a critical role in survival of leukemic stem cells (LSCs) in acute myeloid leukemia (AML). The CD34(+)CD38(-) LSC fraction expresses high levels of FLT3 as well as MCL-1, even compared with normal HSCs. Treatment with FLT3 ligand induced further MCL-1 up-regulation in LSCs in all AML cases tested. Interestingly, the group of samples expressing the highest levels of MCL-1 constituted AML with FLT3-internal tandem duplications (ITD). In FLT3-ITD AML cell lines, cells expressed a high level of MCL-1, and an inhibition of MCL-1 induced their apoptotic cell death. A tyrosine kinase inhibitor suppressed MCL-1 expression, and induced apoptosis that was reversed by the enforced MCL-1 expression. Finally, transduction of FLT3-ITD into HSCs strongly activated MCL-1 expression through its signal transducer and activator of transcription 5 (STAT5)-docking domains. This effect was completely abrogated when STAT5 activation was blocked. Thus, the acquisition of FLT3-ITD ensures LSC survival by up-regulating MCL-1 via constitutive STAT5 activation that is independent of wild-type FLT3 signaling.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Leucemia Mieloide Aguda/genética , Células-Tronco Neoplásicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Fator de Transcrição STAT5/metabolismo , Tirosina Quinase 3 Semelhante a fms/genética , Apoptose/efeitos dos fármacos , Western Blotting , Sobrevivência Celular , Ativação Enzimática/fisiologia , Citometria de Fluxo , Humanos , Leucemia Mieloide Aguda/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sequências de Repetição em Tandem , Regulação para Cima , Tirosina Quinase 3 Semelhante a fms/metabolismo
5.
Cell ; 138(2): 352-65, 2009 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-19592082

RESUMO

Cyclins are regulatory subunits of cyclin-dependent kinases. Cyclin A, the first cyclin ever cloned, is thought to be an essential component of the cell-cycle engine. Mammalian cells encode two A-type cyclins, testis-specific cyclin A1 and ubiquitously expressed cyclin A2. Here, we tested the requirement for cyclin A function using conditional knockout mice lacking both A-type cyclins. We found that acute ablation of cyclin A in fibroblasts did not affect cell proliferation, but led to prolonged expression of another cyclin, cyclin E, across the cell cycle. However, combined ablation of all A- and E-type cyclins extinguished cell division. In contrast, cyclin A function was essential for cell-cycle progression of hematopoietic and embryonic stem cells. Expression of cyclin A is particularly high in these compartments, which might render stem cells dependent on cyclin A, whereas in fibroblasts cyclins A and E play redundant roles in cell proliferation.


Assuntos
Ciclina A/metabolismo , Embrião de Mamíferos/citologia , Células-Tronco Embrionárias/metabolismo , Fibroblastos/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Animais , Ciclina A/genética , Ciclina E/genética , Ciclina E/metabolismo , Camundongos , Camundongos Knockout
6.
Cell Stem Cell ; 1(4): 416-27, 2007 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-18371378

RESUMO

A hierarchical hematopoietic development with myeloid versus lymphoid bifurcation has been proposed downstream of the multipotent progenitor (MPP) stage, based on prospective isolation of progenitors capable of generating only myeloerythroid cells (common myeloid progenitor, CMP) or only lymphocytes (common lymphoid progenitor, CLP). By utilizing GATA-1 and PU.1 transcription factor reporters, here we identified progenitor populations that are precursors for either CMPs or CLPs. Two independent populations expressing either GATA-1 or PU.1 resided within the CD34(+)Sca-1(+)c-Kit(+) MPP fraction. The GATA-1(+) MPP displayed potent myeloerythroid potential without giving rise to lymphocytes, whereas the PU.1(+) MPP showed granulocyte/monocyte/lymphoid-restricted progenitor activity without megakaryocyte/erythroid differentiation. Furthermore, GATA-1(+) and PU.1(+) MPPs possessed huge expansion potential and differentiated into the original CMPs and CLPs, respectively. Thus, the reciprocal activation of GATA-1 and PU.1 primarily organizes the hematopoietic lineage fate decision to form the earliest hematopoietic branchpoint that comprises isolatable myeloerythroid and myelolymphoid progenitor populations.


Assuntos
Linhagem da Célula , Células Precursoras Eritroides/citologia , Fator de Transcrição GATA1/genética , Células-Tronco Hematopoéticas/citologia , Células Progenitoras Linfoides/citologia , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Regulação para Cima/genética , Animais , Antígenos CD34/metabolismo , Ataxina-1 , Ataxinas , Diferenciação Celular , Fator de Transcrição GATA1/metabolismo , Genes Reporter , Linfócitos/citologia , Megacariócitos/citologia , Camundongos , Modelos Biológicos , Células-Tronco Multipotentes/citologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Transativadores/metabolismo
7.
Genes Dev ; 20(21): 3010-21, 2006 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17079688

RESUMO

The mechanism of lineage specification in multipotent stem cells has not been fully understood. We recently isolated progenitors with the eosinophil, basophil, or mast cell lineage potential, all of which originate from granulocyte/monocyte progenitors (GMPs). By using these prospectively purified progenitors, we show here that the expression timing of GATA-2 and CCAAT enhancer-binding protein alpha (C/EBPalpha) can differentially control their lineage commitment. The expression of GATA-2 instructed C/EBPalpha-expressing GMPs to commit exclusively into the eosinophil lineage, while it induced basophil and/or mast cell lineage commitment if C/EBPalpha was suppressed at the GMP stage. Furthermore, simply by switching the order of C/EBPalpha and GATA-2 transduction, even lymphoid-committed progenitors recaptured these developmental processes to be reprogrammed into each of these lineages. We propose that the order of expression of key transcription factors is critical for their interplay to selectively drive lineage specification programs, by which stem cells could generate multiple lineage cells in a hierarchical manner.


Assuntos
Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Fator de Transcrição GATA2/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Hematopoese/genética , Células-Tronco Hematopoéticas/metabolismo , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Diferenciação Celular/genética , Linhagem da Célula/genética , Fator de Transcrição GATA2/genética , Granulócitos/citologia , Granulócitos/metabolismo , Células-Tronco Hematopoéticas/citologia , Mastócitos/citologia , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Células Progenitoras Mieloides/citologia , Células Progenitoras Mieloides/metabolismo
8.
Nat Immunol ; 7(7): 732-9, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16751774

RESUMO

During 'emergency' situations such as infections, host defense requires rapid mobilization of bone marrow granulocyte progenitors. 'Steady-state' granulopoiesis is absolutely dependent on the C/EBPalpha transcription factor, but the transcriptional mechanisms underlying emergency granulopoiesis remain unclear. Here we show that large numbers of granulocytes were generated from C/EBPalpha-deficient progenitors after cytokine stimulation in vivo. Cytokine treatment or fungal infection induced upregulation of C/EBPbeta but not C/EBPalpha or C/EBPepsilon transcripts in granulocyte progenitors, and C/EBPbeta-deficient progenitors showed decreased emergency-induced granulopoiesis in vitro and in vivo. C/EBPbeta inhibited proliferation less severely than did C/EBPalpha. These data suggest a critical function for C/EBPbeta in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/fisiologia , Granulócitos/citologia , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/citologia , Infecções/imunologia , Animais , Animais Congênicos , Proteína alfa Estimuladora de Ligação a CCAAT/deficiência , Proteína alfa Estimuladora de Ligação a CCAAT/fisiologia , Proteína beta Intensificadora de Ligação a CCAAT/deficiência , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/fisiologia , Candidíase/imunologia , Candidíase/fisiopatologia , Ciclo Celular , Diferenciação Celular , Células Cultivadas/metabolismo , Ensaio de Unidades Formadoras de Colônias , Estradiol/farmacologia , Fator Estimulador de Colônias de Granulócitos/genética , Fator Estimulador de Colônias de Granulócitos/fisiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Hematopoese/genética , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Interleucina-3/genética , Interleucina-3/fisiologia , Células K562/citologia , Camundongos , Camundongos Endogâmicos C57BL , Quimera por Radiação , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Estrogênio/genética , Proteínas Recombinantes de Fusão/fisiologia , Transdução Genética , Regulação para Cima
9.
Proc Natl Acad Sci U S A ; 102(50): 18105-10, 2005 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-16330751

RESUMO

Basophils and mast cells, which are selectively endowed with the high-affinity IgE receptor and mediate a range of adaptive and innate immune responses, have an unknown developmental relationship. Here, by evaluating the expression of the beta7 integrin, a molecule that is required for selective homing of mast cell progenitors (MCPs) to the periphery, we identified bipotent progenitors that are capable of differentiating into either cell type in the mouse spleen. These basophil/mast cell progenitors (BMCPs) gave rise to basophils and mast cells at the single-cell level and reconstituted both mucosal and connective tissue mast cells. We also identified the basophil progenitor (BaP) and the MCP in the bone marrow and the gastrointestinal mucosa, respectively. We further show that the granulocyte-related transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) plays a primary role in the fate decision of BMCPs, being expressed in BaPs but not in MCPs. Thus, circulating basophils and tissue mast cells share a common developmental stage at which their fate decision might be controlled principally by C/EBPalpha.


Assuntos
Diferenciação Celular/fisiologia , Linhagem da Célula/fisiologia , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/citologia , Mastócitos/citologia , Animais , Células da Medula Óssea , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Células Cultivadas , Células-Tronco Hematopoéticas/metabolismo , Cadeias beta de Integrinas/metabolismo , Mucosa Intestinal/citologia , Mastócitos/imunologia , Camundongos , Camundongos Mutantes , Ovalbumina/imunologia , Baço/citologia , Trichinella/imunologia
10.
J Exp Med ; 201(12): 1891-7, 2005 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-15955840

RESUMO

Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in the steady-state murine bone marrow. Purified granulocyte/monocyte progenitors (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the single cell level. Within the short-term culture of GMPs, the eosinophil potential was found exclusively in cells activating the transgenic reporter for GATA-1, a transcription factor capable of instructing eosinophil lineage commitment. These GATA-1-activating cells possessed an IL-5Ralpha(+)CD34(+)c-Kit(lo) phenotype. Normal bone marrow cells also contained IL-5Ralpha(+)CD34(+)c-Kit(lo) EoPs that gave rise exclusively to eosinophils. EoPs significantly increased in number in response to helminth infection, suggesting that the EoP stage is physiologically involved in eosinophil production in vivo. EoPs expressed eosinophil-related genes, such as the eosinophil peroxidase and the major basic protein, but did not express basophil/mast cell-related mast cell proteases. The enforced retroviral expression of IL-5Ralpha in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5Ralpha(+) GMPs displayed normal neutrophil/monocyte differentiation in the presence of IL-5 alone. Thus, IL-5Ralpha might be expressed specifically at the EoP stage as a result of commitment into the eosinophil lineage. The newly identified EoPs could be the cellular target in the treatment of a variety of disorders mediated by eosinophils.


Assuntos
Células da Medula Óssea/citologia , Linhagem da Célula/fisiologia , Eosinófilos/citologia , Células Precursoras de Granulócitos/citologia , Animais , Antígenos CD34/metabolismo , Primers do DNA , Proteínas de Ligação a DNA/metabolismo , Fatores de Ligação de DNA Eritroide Específicos , Citometria de Fluxo , Fator de Transcrição GATA1 , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptores de Interleucina/metabolismo , Receptores de Interleucina-5 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/metabolismo , Transdução Genética
11.
Blood ; 106(5): 1590-600, 2005 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-15914556

RESUMO

The PU.1 transcription factor is a key regulator of hematopoietic development, but its role at each hematopoietic stage remains unclear. In particular, the expression of PU.1 in hematopoietic stem cells (HSCs) could simply represent "priming" of genes related to downstream myelolymphoid lineages. By using a conditional PU.1 knock-out model, we here show that HSCs express PU.1, and its constitutive expression is necessary for maintenance of the HSC pool in the bone marrow. Bone marrow HSCs disrupted with PU.1 in situ could not maintain hematopoiesis and were outcompeted by normal HSCs. PU.1-deficient HSCs also failed to generate the earliest myeloid and lymphoid progenitors. PU.1 disruption in granulocyte/monocyte-committed progenitors blocked their maturation but not proliferation, resulting in myeloblast colony formation. PU.1 disruption in common lymphoid progenitors, however, did not prevent their B-cell maturation. In vivo disruption of PU.1 in mature B cells by the CD19-Cre locus did not affect B-cell maturation, and PU.1-deficient mature B cells displayed normal proliferation in response to mitogenic signals including the cross-linking of surface immunoglobulin M (IgM). Thus, PU.1 plays indispensable and distinct roles in hematopoietic development through supporting HSC self-renewal as well as commitment and maturation of myeloid and lymphoid lineages.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Hematopoéticas/citologia , Proteínas Proto-Oncogênicas/fisiologia , Transativadores/fisiologia , Animais , Medula Óssea/metabolismo , Células Cultivadas , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Fígado/embriologia , Fígado/metabolismo , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , Transativadores/deficiência , Transativadores/genética
12.
Science ; 307(5712): 1101-4, 2005 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-15718471

RESUMO

Apoptosis is important in controlling hematopoietic stem cell (HSC) numbers. However, the specific BCL-2 family member(s) that regulate HSC homeostasis are not precisely defined. We tested myeloid leukemia-1 (MCL-1) as an attractive candidate that is highly expressed in HSCs and regulated by growth factor signals. Inducible deletion of Mcl-1 in mice resulted in ablation of bone marrow. This resulted in the loss of early bone marrow progenitor populations, including HSCs. Moreover, growth factors including stem cell factor increased transcription of the Mcl-1 gene and required MCL-1 to augment survival of purified bone marrow progenitors. Deletion of Mcl-1 in other tissues, including liver, did not impair survival. Thus, MCL-1 is a critical and specific regulator essential for ensuring the homeostasis of early hematopoietic progenitors.


Assuntos
Células-Tronco Hematopoéticas/fisiologia , Proteínas de Neoplasias/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Animais , Apoptose , Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Contagem de Células , Linhagem da Célula , Forma Celular , Sobrevivência Celular , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Deleção de Genes , Expressão Gênica , Células-Tronco Hematopoéticas/citologia , Homeostase , Interleucina-6/farmacologia , Fígado/citologia , Fígado/fisiologia , Camundongos , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteínas de Neoplasias/genética , Poli I-C/farmacologia , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Fator de Células-Tronco/farmacologia , Transdução Genética
13.
Immunity ; 21(1): 43-53, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15345219

RESUMO

The developmental origin of type I interferon (IFN)-producing plasmacytoid dendritic cells (PDCs) is controversial. In particular, the rearrangement of immunoglobulin heavy chain (IgH) genes in murine PDCs and the expression of pre-T cell receptor alpha (pTalpha) gene by human PDCs were proposed as evidence for their "lymphoid" origin. Here we demonstrate that PDCs capable of IFN production develop efficiently from both myeloid- and lymphoid-committed progenitors. Rearranged IgH genes as well as RAG transcripts were found in both myeloid- and lymphoid-derived PDCs. The human pTalpha transgenic reporter was activated in both myeloid- and lymphoid-derived PDCs at a level comparable to pre-T cells. PDCs were the only cell population that activated murine RAG1 knockin and human pTalpha transgenic reporters outside the lymphoid lineage. These results highlight a unique developmental program of PDCs that distinguishes them from other cell types including conventional dendritic cells.


Assuntos
Células da Medula Óssea/fisiologia , Células Dendríticas/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Plasmócitos/fisiologia , Animais , Diferenciação Celular , Linhagem da Célula , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Proteínas de Homeodomínio/metabolismo , Humanos , Interferon Tipo I/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos T alfa-beta
14.
Immunity ; 19(3): 451-62, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14499119

RESUMO

GATA-1 is an essential transcription factor for megakaryocyte and erythrocyte (MegE) development. Here we show that hematopoietic progenitors can be reprogrammed by the instructive action of GATA-1. Enforced expression of GATA-1 in hematopoietic stem cells led to loss of self-renewal activity and the exclusive generation of MegE lineages. Strikingly, ectopic GATA-1 reprogrammed common lymphoid progenitors as well as granulocyte/monocyte (GM) progenitors to differentiate into MegE lineages, while inhibiting normal lymphoid or GM differentiation. GATA-1 upregulated critical MegE-related transcription factors such as FOG-1 and GATA-2 in lymphoid and GM progenitors, and their MegE development did not require "permissive" erythropoietin signals. Furthermore, GATA-1 induced apoptosis of proB and myelomonocytic cells, which could not be prevented by enforced permissive Bcl-2 or myeloid cytokine signals. Thus, GATA-1 specifically instructs MegE commitment while excluding other fate outcomes in stem and progenitor cells, suggesting that regulation of GATA-1 is critical in maintaining multilineage homeostasis.


Assuntos
Diferenciação Celular/fisiologia , Proteínas de Ligação a DNA/metabolismo , Eritrócitos/metabolismo , Megacariócitos/metabolismo , Células Progenitoras Mieloides/metabolismo , Fatores de Transcrição/metabolismo , Animais , Apoptose/fisiologia , Proteínas de Transporte/metabolismo , Fatores de Ligação de DNA Eritroide Específicos , Fator de Transcrição GATA1 , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/fisiologia
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