Hmga2 Promotes Neural Stem Cell Self-Renewal in Young but Not Old Mice by Reducing p16(Ink4a) and p19(Arf) Expression

Cited 496 time in webofscience Cited 495 time in scopus
  • Hit : 649
  • Download : 68
Stem cells persist throughout life in diverse tissues by undergoing self-renewing divisions. Self-renewal capacity declines with age, partly because of increasing expression of the tumor suppressor p16(Ink4a). We discovered that the Hmga2 transcriptional regulator is highly expressed in fetal neural stem cells but that expression declines with age. This decrease is partly caused by the increasing expression of let-7b microRNA, which is known to target HMGA2. Hmga2-deficient mice show reduced stem cell numbers and self-renewal throughout the central and peripheral nervous systems of fetal and young-adult mice but not old-adult mice. Furthermore, p16(Ink4a) and p19(Arf) expression were increased in Hmga2-deficient fetal and young-adult stem cells, and deletion of p16(Ink4a) and/or p19(Arf) partially restored self-renewal capacity. let-7b overexpression reduced Hmga2 and increased p16(Ink4a)/p19(Arf) expression. Hmga2 thus promotes fetal and young-adult stem cell self-renewal by decreasing p16(Ink4a)/p19(Arf) expression. Changes in let-7 and Hmga2 expression during aging contribute to the decline in neural stem cell function.
Publisher
CELL PRESS
Issue Date
2008-10
Language
English
Article Type
Article
Keywords

TUMOR SUPPRESSION; INK4A LOCUS; DEPENDENCE DISTINGUISHES; TRANSGENIC MICE; BMI-1; MOUSE; PROLIFERATION; PROTEINS; SENESCENCE; GENE

Citation

CELL, v.135, no.2, pp.227 - 239

ISSN
0092-8674
DOI
10.1016/j.cell.2008.09.017
URI
http://hdl.handle.net/10203/13440
Appears in Collection
MSE-Journal Papers(저널논문)
Files in This Item
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 496 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0