Cdc42 Activity Regulates Hematopoietic Stem Cell Aging and Rejuvenation

被引：446

作者：

Florian, Maria Carolina ^{[1
]}

Doerr, Karin ^{[1
]}

Niebel, Anja ^{[1
]}

Daria, Deidre ^{[1
]}

Schrezenmeier, Hubert ^{[2
]}

Rojewski, Markus ^{[2
]}

Filippi, Marie-Dominique ^{[3
,4
]}

Hasenberg, Anja ^{[5
]}

Gunzer, Matthias ^{[5
]}

Scharffetter-Kochanek, Karin ^{[1
]}

Zheng, Yi ^{[3
,4
]}

Geiger, Hartmut ^{[1
,3
,4
]}

机构：

[1] Univ Ulm, Dept Dermatol & Allerg Dis, D-89091 Ulm, Germany

[2] Univ Ulm, Inst Clin Transfus Med & Immunogenet Ulm, D-89091 Ulm, Germany

[3] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA

[4] Univ Cincinnati, Cincinnati, OH 45229 USA

[5] Univ Duisburg Essen, Univ Hosp, Inst Expt Immunol & Imaging, D-45141 Essen, Germany

来源：

CELL STEM CELL | 2012年 / 10卷 / 05期

关键词：

EPIGENETIC INHERITANCE; POLARITY; DIVISION; BLOOD; DIFFERENTIATION; TRANSPLANTATION; ACTIVATION; EXPRESSION; PROTEINS; UNDERLIE;

D O I：

10.1016/j.stem.2012.04.007

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

The decline in hematopoietic function seen during aging involves a progressive reduction in the immune response and an increased incidence of myeloid malignancy, and has been linked to aging of hematopoietic stem cells (HSCs). The molecular mechanisms underlying HSC aging remain unclear. Here we demonstrate that elevated activity of the small RhoGTPase Cdc42 in aged HSCs is causally linked to HSC aging and correlates with a loss of polarity in aged HSCs. Pharmacological inhibition of Cdc42 activity functionally rejuvenates aged HSCs, increases the percentage of polarized cells in an aged HSC population, and restores the level and spatial distribution of histone H4 lysine 16 acetylation to a status similar to that seen in young HSCs. Our data therefore suggest a mechanistic role for Cdc42 activity in HSC biology and epigenetic regulation, and identify Cdc42 activity as a pharmacological target for ameliorating stem cell aging.

引用

页码：520 / 530

页数：11

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