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Cell Death Dis ; 9(5): 502, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29717132

RESUMO

The adult olfactory mucosa, a highly regenerative tissue with unique life-long neurogenesis ability, is thought to harbor a naïve yet tightly controlled stem cell population. It will provide unique benefits in various stem cell-based therapies, such as stroke treatment. Here, we identified a subpopulation of adult pluripotent-like olfactory stem cells (APOSCs), which were modulated by an epigenetic repressor of CBX7. APOSCs form a floating sphere, express pluripotency markers Nanog, Oct-4, Sox-2, and SSEA-4 and show alkaline phosphatase activity. In addition, APOSCs display self-renewal and a pluripotent potential to differentiate into all three germ layers. Moreover, APOSCs coexpress pluripotency markers with CBX7. Within their natural niche, APOSCs from CBX7+/+ mice responded promptly to either spontaneous or injury-induced tissue regeneration. However, APOSCs from CBX7-/- mice manifested an impaired self-renewal and differentiation potential. Similarly, in vitro-cultivated CBX7-/- APOSCs underwent premature senescence, whereas CBX7+/+ APOSCs still actively divided, indicating that CBX7 is required for the self-renewal of APOSCs. Intracerebral implantation of APOSCs improved the stroke-mediated neurological dysfunction in rodents. These findings indicate that CBX7 plays a critical role in the regenerative properties of APOSCs and indicate the safety and feasibility of implantation of autologous APOSCs in stroke treatment.


Assuntos
Epigênese Genética , Mucosa Olfatória/metabolismo , Células-Tronco Pluripotentes/metabolismo , Complexo Repressor Polycomb 1/genética , Acidente Vascular Cerebral/genética , Animais , Diferenciação Celular , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Homeobox Nanog/genética , Proteína Homeobox Nanog/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Mucosa Olfatória/citologia , Células-Tronco Pluripotentes/citologia , Complexo Repressor Polycomb 1/metabolismo , Ratos , Ratos Sprague-Dawley , Regeneração/genética , Transdução de Sinais , Antígenos Embrionários Estágio-Específicos/genética , Antígenos Embrionários Estágio-Específicos/metabolismo , Transplante de Células-Tronco , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapia , Transplante Autólogo
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