Nuclear envelope defects cause stem cell dysfunction in premature-aging mice.
Nuclear envelope defects cause stem cell dysfunction in premature-aging mice.
复制标题
核包膜缺陷会导致过早小鼠的干细胞功能障碍。
DOI：
10.1083/jcb.200801096
复制
发表时间：
2008-04-07
影响因子：
7.8
通讯作者：
Lopez-Otin, Carlos
中科院分区：
文献类型：
--
作者：
Espada, Jesus;Varela, Ignacio;Flores, Ignacio;Ugalde, Alejandro P.;Cadinanos, Juan;Pendas, Alberto M.;Stewart, Colin L.;Tryggvason, Karl;Blasco, Maria A.;Freije, Jose M. P.;Lopez-Otin, Carlos
核纤层改变发生在生理老化和早衰综合征中。由于衰老也与异常的干细胞稳态有关，我们假设核膜的改变可能对干细胞区室产生重要影响。为了评估这一假设，我们研究了Zmpste 24无效的早衰小鼠，表现出核板层缺陷的干细胞的数量和功能能力。我们发现，Zmpste 24缺陷导致表皮干细胞的数量和增殖能力的改变。这些变化与异常核结构的隆突细胞和增加其支持细胞在毛球区域的凋亡。这些改变在Zmpste 24 −/− Lmna +/−突变小鼠中得到挽救，这些小鼠不表现出早衰样症状。我们还报告了与干细胞行为调控有关的分子信号通路，如Wnt和小眼症转录因子，在Zmpste 24 −/−小鼠中发生了改变。这些发现建立了与年龄相关的核膜缺陷和干细胞功能障碍之间的联系。
Nuclear lamina alterations occur in physiological aging and in premature aging syndromes. Because aging is also associated with abnormal stem cell homeostasis, we hypothesize that nuclear envelope alterations could have an important impact on stem cell compartments. To evaluate this hypothesis, we examined the number and functional competence of stem cells in Zmpste24-null progeroid mice, which exhibit nuclear lamina defects. We show that Zmpste24 deficiency causes an alteration in the number and proliferative capacity of epidermal stem cells. These changes are associated with an aberrant nuclear architecture of bulge cells and an increase in apoptosis of their supporting cells in the hair bulb region. These alterations are rescued in Zmpste24 −/− Lmna +/− mutant mice, which do not manifest progeroid symptoms. We also report that molecular signaling pathways implicated in the regulation of stem cell behavior, such as Wnt and microphthalmia transcription factor, are altered in Zmpste24 −/− mice. These findings establish a link between age-related nuclear envelope defects and stem cell dysfunction.
登录
查看更多内容
影响因子：
4.6
作者：
Filesi, I;Gullotta, F;Novelli, G
通讯作者：
Novelli, G
影响因子：
4.3
作者：
Cadiñanos, J;Varela, I;Freije, JMP
通讯作者：
Freije, JMP
影响因子：
56.9
作者：
Flores, I;Cayuela, ML;Blasco, MA
通讯作者：
Blasco, MA
影响因子：
10.5
作者：
Godwin, AR;Capecchi, MR
通讯作者：
Capecchi, MR
影响因子：
64.5
作者：
COTSARELIS, G;SUN, TT;LAVKER, RM
通讯作者：
LAVKER, RM