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1.
PLoS One ; 2(4): e394, 2007 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-17460761

RESUMO

BACKGROUND: The spontaneous emergence of phenotypic heterogeneity in clonal populations of mammalian cells in vitro is a rule rather than an exception. We consider two simple, mutually non-exclusive models that explain the generation of diverse cell types in a homogeneous population. In the first model, the phenotypic switch is the consequence of extrinsic factors. Initially identical cells may become different because they encounter different local environments that induce adaptive responses. According to the second model, the phenotypic switch is intrinsic to the cells that may occur even in homogeneous environments. PRINCIPAL FINDINGS: We have investigated the "extrinsic" and the "intrinsic" mechanisms using computer simulations and experimentation. First, we simulated in silico the emergence of two cell types in a clonal cell population using a multiagent model. Both mechanisms produced stable phenotypic heterogeneity, but the distribution of the cell types was different. The "intrinsic" model predicted an even distribution of the rare phenotype cells, while in the "extrinsic" model these cells formed small clusters. The key predictions of the two models were confronted with the results obtained experimentally using a myogenic cell line. CONCLUSIONS: The observations emphasize the importance of the "ecological" context and suggest that, consistently with the "extrinsic" model, local stochastic interactions between phenotypically identical cells play a key role in the initiation of phenotypic switch. Nevertheless, the "intrinsic" model also shows some other aspects of reality: The phenotypic switch is not triggered exclusively by the local environmental variations, but also depends to some extent on the phenotypic intrinsic robustness of the cells.


Assuntos
Células Clonais , Humanos , Técnicas In Vitro , Modelos Biológicos , Fenótipo
2.
BMC Mol Biol ; 5: 4, 2004 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-15200685

RESUMO

BACKGROUND: Poly (ADP-ribosyl)ation is a covalent modification of many nuclear proteins. It has a strong chromatin modifying potential involved in DNA repair, transcription and replication. Its role during preimplantation development is unknown. RESULTS: We have observed strong but transient synthesis of poly ADP-ribose polymers on decondensing chromosomes of fertilized and parthenogenetically activated mouse oocytes. Inhibition of this transient upregulation with a specific enzyme inhibitor, 3-aminobenzamide, has long-term effects on the postimplantation development of the embryos. In addition, inhibition of poly (ADP-ribosyl)ation at the 4-8 cell stage selectively blocks morula compaction. CONCLUSION: These observations suggest that poly (ADP-ribosyl)ation is involved in the epigenetic chromatin remodeling in the zygote.


Assuntos
Blastocisto/metabolismo , Desenvolvimento Embrionário e Fetal/fisiologia , Poli Adenosina Difosfato Ribose/fisiologia , Animais , Benzamidas/farmacologia , Blastocisto/química , Blastocisto/enzimologia , Montagem e Desmontagem da Cromatina/fisiologia , Cruzamentos Genéticos , Embrião de Mamíferos/química , Embrião de Mamíferos/embriologia , Epigênese Genética/efeitos dos fármacos , Epigênese Genética/fisiologia , Feminino , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Mórula/efeitos dos fármacos , Mórula/enzimologia , Mórula/metabolismo , Oócitos/química , Oócitos/enzimologia , Oócitos/crescimento & desenvolvimento , Poli Adenosina Difosfato Ribose/imunologia , Poli Adenosina Difosfato Ribose/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases , Poli(ADP-Ribose) Polimerases/fisiologia , Polímeros/metabolismo , Zigoto/enzimologia , Zigoto/crescimento & desenvolvimento , Zigoto/fisiologia
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