Nuclear envelope defects cause stem cell dysfunction in premature-aging mice

被引：127

作者：

Espada, Jesus ^{[1
]}

Varela, Ignacio ^{[1
]}

Flores, Ignacio ^{[2
]}

Ugalde, Alejandro P. ^{[1
]}

Cadinanos, Juan ^{[1
]}

Pendas, Alberto M. ^{[1
]}

Stewart, Colin L. ^{[3
]}

Tryggvason, Karl ^{[4
]}

Blasco, Maria A. ^{[2
]}

Freije, Jose M. P. ^{[1
]}

Lopez-Otin, Carlos ^{[1
]}

机构：

[1] Univ Oviedo, Inst Univ Oncol, Fac Med, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain

[2] Spanish Natl Canc Res Ctr, Mol Oncol Program, Telomeres & Telomerase Grp, Madrid 28029, Spain

[3] Natl Canc Inst, Ft Detrick, MD 21702 USA

[4] Karolinska Inst, Dept Biophys & Biochem, Div Matrix Biol, SE-17177 Stockholm, Sweden

来源：

JOURNAL OF CELL BIOLOGY | 2008年 / 181卷 / 01期

关键词：

D O I：

10.1083/jcb.200801096

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：27 / 35

页数：9

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