RESUMO
In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage. We found that these developmentally arrested T-cell precursors gave rise to functional B cells upon transfer to immunodeficient mice. We further demonstrated that the arrest was almost completely canceled by additional deletion of Pax5 These results indicate that the maintenance of T-cell fate critically requires epigenetic suppression of the B-lineage gene program.
Assuntos
Linfócitos B/citologia , Transformação Celular Neoplásica/genética , Epigênese Genética/genética , Inativação Gênica , Proteínas do Grupo Polycomb/metabolismo , Linfócitos T/citologia , Animais , Linhagem da Célula , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento , Cadeias Pesadas de Imunoglobulinas/genética , Camundongos Endogâmicos C57BL , Fator de Transcrição PAX5/genética , Fator de Transcrição PAX5/metabolismo , Complexo Repressor Polycomb 1/genética , Regiões Promotoras Genéticas/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
Dyspnea is one of the most common problems we encounter in the palliative care setting of patients with life-threatening illness including malignancy. Dyspnea is considered especially a troublesome symptom in the management of in-home hospice care services. We examined effects of anti-cholinergic agents against such symptoms associated with dyspnea in patients with serious illness treated at home. The effectiveness was observed in 51% of patients who were given anti-cholinergic drugs. According to the outcome of this study, anti-cholinergic drugs may be effective for alleviating the suffering of terminally-ill patients due to dyspnea. Further investigation would be expected to clarify the usefulness of anti-cholinergic agents in the field of palliative care.