Bmi-1通过抑制p16Ink4a和p19Arf衰老途径来促进神经干细胞自我更新和神经发育，但不影响小鼠的生长和存活。
Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways.
作者信息
Molofsky Anna V, He Shenghui, Bydon Mohammad, Morrison Sean J, Pardal Ricardo
机构信息
Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-0934, USA.
出版信息
Genes Dev. 2005 Jun 15;19(12):1432-7. doi: 10.1101/gad.1299505.
Abstract
Bmi-1 is required for the post-natal maintenance of stem cells in multiple tissues including the central nervous system (CNS) and peripheral nervous system (PNS). Deletion of Ink4a or Arf from Bmi-1(-/-) mice partially rescued stem cell self-renewal and stem cell frequency in the CNS and PNS, as well as forebrain proliferation and gut neurogenesis. Arf deficiency, but not Ink4a deficiency, partially rescued cerebellum development, demonstrating regional differences in the sensitivity of progenitors to p16Ink4a and p19Arf. Deletion of both Ink4a and Arf did not affect the growth or survival of Bmi-1(-/-) mice or completely rescue neural development. Bmi-1 thus prevents the premature senescence of neural stem cells by repressing Ink4a and Arf, but additional pathways must also function downstream of Bmi-1.
摘要
Bmi-1是包括中枢神经系统（CNS）和外周神经系统（PNS）在内的多种组织中干细胞产后维持所必需的。从Bmi-1（-/-）小鼠中删除Ink4a或Arf可部分挽救CNS和PNS中的干细胞自我更新和干细胞频率，以及前脑增殖和肠道神经发生。Arf缺陷而非Ink4a缺陷可部分挽救小脑发育，表明祖细胞对p16Ink4a和p19Arf的敏感性存在区域差异。同时删除Ink4a和Arf并不影响Bmi-1（-/-）小鼠的生长或存活，也不能完全挽救神经发育。因此，Bmi-1通过抑制Ink4a和Arf来防止神经干细胞过早衰老，但在Bmi-1下游必定还有其他途径发挥作用。
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