期刊
GENES & DEVELOPMENT
卷 19, 期 12, 页码 1432-1437出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1299505
关键词
Bmi-1; neural crest; stem cell; p16(Ink4a); p19(Arf); self-renewal
资金
- NCI NIH HHS [CA46592, P30 CA046592] Funding Source: Medline
- NIAMS NIH HHS [P30 AR48310, P30 AR048310, P60-AR20557] Funding Source: Medline
- NIDDK NIH HHS [5P60-DK20572, P60 DK020572] Funding Source: Medline
- NINDS NIH HHS [R01 NS040750, F30 NS048642, R01 NS40750] Funding Source: Medline
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 p16(Ink4a) and p19(Arf). 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.
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