Hmga2 Promotes Neural Stem Cell Self-Renewal in Young but Not Old Mice by Reducing p16Ink4a and p19Arf Expression

被引：514

作者：

Nishino, Jinsuke ^{[1
,2
]}

Kim, Injune ^{[1
,2
]}

Chada, Kiran ^{[3
]}

Morrison, Sean J. ^{[1
,2
]}

机构：

[1] Univ Michigan, Howard Hughes Med Inst, Inst Life Sci, Dept Internal Med, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA

[3] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08554 USA

来源：

CELL | 2008年 / 135卷 / 02期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.cell.2008.09.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：227 / 239

页数：13

共 40 条

[1] Transgenic mice expressing a truncated form of the high mobility group I-C protein develop adiposity and an abnormally high prevalence of lipomas [J].