在我們的整個生命過程當(dāng)中,，干細胞都通過自我更新的分裂過程一直維持存在,。干細胞的這種自我更新、維持的能力會隨著年齡的增長而不斷減弱,，造成這一現(xiàn)象的原因部分在于腫瘤抑制子p16Ink4a的表達增強,。在2008年10月17日出版的《細胞》（Cell）上，來自美國密歇根大學(xué)干細胞生物中心的科學(xué)家Nishino等人以封面文章的形式發(fā)表了他們在p16Ink4a的表達方面的最新研究結(jié)果,。
文章中作者表示,，他們發(fā)現(xiàn)在胚胎神經(jīng)干細胞中，一種轉(zhuǎn)錄調(diào)節(jié)子Hmga2得到高度的表達,，然而隨著個體年齡的增長,，這種表達將會逐漸減弱,。在研究中科學(xué)家還發(fā)現(xiàn)，造成Hmga2表達減弱的部分原因在于小分子RNA let-7b表達的增加,，科學(xué)家已經(jīng)知道let-7b的作用目標(biāo)正是Hmga2,。缺乏Hmga2的小鼠在胚胎以及年幼時期中樞和周圍神經(jīng)系統(tǒng)都表現(xiàn)出干細胞數(shù)量的減少,，以及自我更新的減弱,，然而這種現(xiàn)象不會發(fā)生于年長的成年小鼠。
此外科學(xué)家還發(fā)現(xiàn),，在缺乏Hmga2的胚胎以及幼年小鼠干細胞中,，p16Ink4a和p19Arf的表達都會有所增加，而去除p16Ink4a和/或p19Arf能部分恢復(fù)干細胞自我更新的能力,。let-7b的過度表達能減少Hmga2表達,，同時促進p16Ink4a和p19Arf的表達。
因此作者認(rèn)為,，Hmga2能通過降低p16Ink4a和p19Arf的表達來實現(xiàn)促進胚胎,、幼年小鼠干細胞自我更新的目的。而衰老過程中l(wèi)et-7和Hmga2的改變是導(dǎo)致神經(jīng)干細胞功能衰退的原因,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell,，Vol 135, 227-239, 17 October 2008，Jinsuke Nishino, Sean J. Morrison
Hmga2 Promotes Neural Stem Cell Self-Renewal in Young but Not Old Mice by Reducing p16Ink4a and p19Arf Expression
Jinsuke Nishino,1 Injune Kim,1 Kiran Chada,2 and Sean J. Morrison1,
1 Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA
2 Department of Biochemistry, University of Medicine and Dentistry, Robert Wood Johnson Medical School, Piscataway, NJ 08554, USA
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 p16Ink4a. 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, p16Ink4a and p19Arf expression were increased in Hmga2-deficient fetal and young-adult stem cells, and deletion of p16Ink4a and/or p19Arf partially restored self-renewal capacity. let-7b overexpression reduced Hmga2 and increased p16Ink4a/p19Arf expression. Hmga2 thus promotes fetal and young-adult stem cell self-renewal by decreasing p16Ink4a/p19Arf expression. Changes in let-7 and Hmga2 expression during aging contribute to the decline in neural stem cell function.
