在我们的整个生命过程当中，干细胞都通过自我更新的分裂过程一直维持存在。干细胞的这种自我更新、维持的能力会随着年龄的增长而不断减弱，造成这一现象的原因部分在于肿瘤抑制子p16Ink4a的表达增强。在2008年10月17日出版的《细胞》（Cell）上，来自美国密歇根大学干细胞生物中心的科学家Nishino等人以封面文章的形式发表了他们在p16Ink4a的表达方面的最新研究结果。
文章中作者表示，他们发现在胚胎神经干细胞中，一种转录调节子Hmga2得到高度的表达，然而随着个体年龄的增长，这种表达将会逐渐减弱。在研究中科学家还发现，造成Hmga2表达减弱的部分原因在于小分子RNA let-7b表达的增加，科学家已经知道let-7b的作用目标正是Hmga2。缺乏Hmga2的小鼠在胚胎以及年幼时期中枢和周围神经系统都表现出干细胞数量的减少，以及自我更新的减弱，然而这种现象不会发生于年长的成年小鼠。
此外科学家还发现，在缺乏Hmga2的胚胎以及幼年小鼠干细胞中，p16Ink4a和p19Arf的表达都会有所增加，而去除p16Ink4a和/或p19Arf能部分恢复干细胞自我更新的能力。let-7b的过度表达能减少Hmga2表达，同时促进p16Ink4a和p19Arf的表达。
因此作者认为，Hmga2能通过降低p16Ink4a和p19Arf的表达来实现促进胚胎、幼年小鼠干细胞自我更新的目的。而衰老过程中let-7和Hmga2的改变是导致神经干细胞功能衰退的原因。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
