Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
1.
Nature ; 448(7150): 191-5, 2007 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-17597762

RESUMO

Although the first mouse embryonic stem (ES) cell lines were derived 25 years ago using feeder-layer-based blastocyst cultures, subsequent efforts to extend the approach to other mammals, including both laboratory and domestic species, have been relatively unsuccessful. The most notable exceptions were the derivation of non-human primate ES cell lines followed shortly thereafter by their derivation of human ES cells. Despite the apparent common origin and the similar pluripotency of mouse and human embryonic stem cells, recent studies have revealed that they use different signalling pathways to maintain their pluripotent status. Mouse ES cells depend on leukaemia inhibitory factor and bone morphogenetic protein, whereas their human counterparts rely on activin (INHBA)/nodal (NODAL) and fibroblast growth factor (FGF). Here we show that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells. Our results demonstrate that activin/Nodal signalling has an evolutionarily conserved role in the derivation and the maintenance of pluripotency in these novel stem cells. Epiblast stem cells provide a valuable experimental system for determining whether distinctions between mouse and human embryonic stem cells reflect species differences or diverse temporal origins.


Assuntos
Embrião de Mamíferos/citologia , Células-Tronco Embrionárias/citologia , Células-Tronco Pluripotentes/citologia , Ativinas/metabolismo , Animais , Técnicas de Cultura de Células , Linhagem Celular , Meios de Cultura/química , Implantação do Embrião , Células-Tronco Embrionárias/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Análise de Sequência com Séries de Oligonucleotídeos , Células-Tronco Pluripotentes/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Transdução de Sinais
2.
Dev Biol ; 341(1): 84-94, 2010 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-19941846

RESUMO

The vertebrate head is an extremely complicated structure: development of the head requires tissue-tissue interactions between derivates of all the germ layers and coordinated morphogenetic movements in three dimensions. In this review, we highlight a number of recent embryological studies, using chicken, frog, zebrafish and mouse, which have identified crucial signaling centers in the embryonic face. These studies demonstrate how small variations in growth factor signaling can lead to a diversity of phenotypic outcomes. We also discuss novel genetic studies, in human, mouse and zebrafish, which describe cell biological mechanisms fundamental to the growth and morphogenesis of the craniofacial skeleton. Together, these findings underscore the complex interactions leading to species-specific morphology. These and future studies will improve our understanding of the genetic and environmental influences underlying human craniofacial anomalies.


Assuntos
Ossos Faciais/embriologia , Crânio/embriologia , Animais , Humanos
3.
Mech Dev ; 119(2): 191-200, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12464432

RESUMO

Two regions expressing Hex in the early gastrula contribute to organizing the anterior of the vertebrate embryo. In Xenopus, these include the anterior yolky endoderm and the suprablastoporal endoderm (SBE), which is fated to form the epithelial lining of the gut. These tissues may correspond to the anterior visceral endoderm and anterior definitive endoderm of amniotes. Genetic studies in mice have demonstrated the important roles of these tissues in producing anterior identity in the adjacent neural ectoderm. In Xenopus, both the anterior endoderm and the SBE have anterior inducing properties; furthermore, the SBE can organize a full anterior-posterior axis. Inhibition of Xhex function shows that both these Xhex-expressing endodermal tissues are required for anterior development in Xenopus.


Assuntos
Endoderma/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/biossíntese , Animais , Sequência de Bases , Padronização Corporal , Sistema Digestório/embriologia , Epitélio/embriologia , Hibridização In Situ , Camundongos , Camundongos Knockout , Microscopia de Fluorescência , Dados de Sequência Molecular , Oligonucleotídeos Antissenso/farmacologia , Plasmídeos/metabolismo , Biossíntese de Proteínas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Fatores de Transcrição , Xenopus , Proteínas de Xenopus
4.
PLoS One ; 4(6): e6082, 2009 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-19564924

RESUMO

Human embryonic stem cells have unique value for regenerative medicine, as they are capable of differentiating into a broad variety of cell types. Therefore, defining the signalling pathways that control early cell fate decisions of pluripotent stem cells represents a major task. Moreover, modelling the early steps of embryonic development in vitro may provide the best approach to produce cell types with native properties. Here, we analysed the function of key developmental growth factors such as Activin, FGF and BMP in the control of early cell fate decisions of human pluripotent stem cells. This analysis resulted in the development and validation of chemically defined culture conditions for achieving specification of human embryonic stem cells into neuroectoderm, mesendoderm and into extra-embryonic tissues. Importantly, these defined culture conditions are devoid of factors that could obscure analysis of developmental mechanisms or render the resulting tissues incompatible with future clinical applications. Importantly, the growth factor roles defined using these culture conditions similarly drove differentiation of mouse epiblast stem cells derived from post implantation embryos, thereby reinforcing the hypothesis that epiblast stem cells share a common embryonic identity with human pluripotent stem cells. Therefore the defined growth factor conditions described here represent an essential step toward the production of mature cell types from pluripotent stem cells in conditions fully compatible with clinical use ant also provide a general approach for modelling the early steps of mammalian embryonic development.


Assuntos
Diferenciação Celular , Linhagem da Célula , Células-Tronco Embrionárias/citologia , Camadas Germinativas/citologia , Células-Tronco/citologia , Animais , Proteína Morfogenética Óssea 4/metabolismo , Ectoderma/metabolismo , Células-Tronco Embrionárias/fisiologia , Endoderma/metabolismo , Humanos , Mesoderma/metabolismo , Camundongos , Modelos Biológicos , Transdução de Sinais
5.
Development ; 136(8): 1339-49, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19279133

RESUMO

The pluripotent status of embryonic stem cells (ESCs) confers upon them the capacity to differentiate into the three primary germ layers, ectoderm, mesoderm and endoderm, from which all the cells of the adult body are derived. An understanding of the mechanisms controlling pluripotency is thus essential for driving the differentiation of human pluripotent cells into cell types useful for clinical applications. The Activin/Nodal signalling pathway is necessary to maintain pluripotency in human ESCs and in mouse epiblast stem cells (EpiSCs), but the molecular mechanisms by which it achieves this effect remain obscure. Here, we demonstrate that Activin/Nodal signalling controls expression of the key pluripotency factor Nanog in human ESCs and in mouse EpiSCs. Nanog in turn prevents neuroectoderm differentiation induced by FGF signalling and limits the transcriptional activity of the Smad2/3 cascade, blocking progression along the endoderm lineage. This negative-feedback loop imposes stasis in neuroectoderm and mesendoderm differentiation, thereby maintaining the pluripotent status of human ESCs and mouse EpiSCs.


Assuntos
Ativinas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Proteína Nodal/metabolismo , Células-Tronco Pluripotentes/metabolismo , Transdução de Sinais , Animais , Biomarcadores , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular , Células Cultivadas , Fator 2 de Crescimento de Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Camadas Germinativas/embriologia , Camadas Germinativas/metabolismo , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Proteína Homeobox Nanog , Neurônios/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA