RESUMO
Recent evidence indicates that mouse and human embryonic stem cells (ESCs) are fixed at different developmental stages, with the former positioned earlier. We show that a narrow concentration of the naturally occurring short-chain fatty acid, sodium butyrate, supports the extensive self-renewal of mouse and human ESCs, while promoting their convergence toward an intermediate stem cell state. In response to butyrate, human ESCs regress to an earlier developmental stage characterized by a gene expression profile resembling that of mouse ESCs, preventing precocious Xist expression while retaining the ability to form complex teratomas in vivo. Other histone deacetylase inhibitors (HDACi) also support human ESC self-renewal. Our results indicate that HDACi can promote ESC self-renewal across species, and demonstrate that ESCs can toggle between alternative states in response to environmental factors.
Assuntos
Butiratos/farmacologia , Diferenciação Celular , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/fisiologia , Inibidores de Histona Desacetilases , Animais , Células-Tronco Embrionárias/enzimologia , Inibidores Enzimáticos/farmacologia , Perfilação da Expressão Gênica , Histona Desacetilases/metabolismo , Humanos , Camundongos , RNA Longo não Codificante , RNA não Traduzido/metabolismoRESUMO
Müller glia can serve as a source of new neurons after retinal damage in both fish and birds. Investigations of regeneration in the mammalian retina in vitro have provided some evidence that Müller glia can proliferate after retinal damage and generate new rods; however, the evidence that this occurs in vivo is not conclusive. We have investigated whether Müller glia have the potential to generate neurons in the mouse retina in vivo by eliminating ganglion and amacrine cells with intraocular NMDA injections and stimulating Müller glial to re-enter the mitotic cycle by treatment with specific growth factors. The proliferating Müller glia dedifferentiate and a subset of these cells differentiated into amacrine cells, as defined by the expression of amacrine cell-specific markers Calretinin, NeuN, Prox1, and GAD67-GFP. These results show for the first time that the mammalian retina has the potential to regenerate inner retinal neurons in vivo.
Assuntos
Regeneração Nervosa/fisiologia , Neuroglia/citologia , Neurônios/citologia , Retina/citologia , Retina/fisiologia , Células Amácrinas/citologia , Células Amácrinas/metabolismo , Animais , Biomarcadores/metabolismo , Calbindina 2 , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Linhagem da Célula/fisiologia , Proteínas de Ligação a DNA , Denervação , Agonistas de Aminoácidos Excitatórios/toxicidade , Glutamato Descarboxilase/metabolismo , Proteínas de Fluorescência Verde , Proteínas de Homeodomínio/metabolismo , Camundongos , Camundongos Transgênicos , N-Metilaspartato/toxicidade , Proteínas do Tecido Nervoso/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Proteínas Nucleares/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
Failure of the glenoid component is the most common indication for late revision of a total shoulder arthroplasty (TSA). This is the first study to characterize the deterioration in patient self-assessment of shoulder function occurring with glenoid component failure at times remote from the index surgery. Of 115 total shoulders, 11 had revision by the original surgeon for isolated glenoid loosening. Simple Shoulder Test scores averaged 4.4 before TSA, rose to a mean of 11.3 after surgery, and fell to a mean of 4.6 before revision for glenoid loosening performed at a mean of 7 years after TSA. All shoulders showed a drop of at least 3 points between the peak Simple Shoulder Test score and the prerevision Simple Shoulder Test score. Periodic self-assessment of shoulder function may offer a method of screening patients for the possibility of late glenoid component failure.