Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation.
Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation.
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DOI：
10.1016/j.stem.2012.04.007
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发表时间：
2012-05-04
期刊：
影响因子：
23.9
通讯作者：
Geiger, Hartmut
中科院分区：
文献类型：
--
作者：
Florian, Maria Carolina;Doerr, Karin;Niebel, Anja;Daria, Deidre;Schrezenmeier, Hubert;Rojewski, Markus;Filippi, Marie-Dominique;Hasenberg, Anja;Gunzer, Matthias;Scharffetter-Kochanek, Karin;Zheng, Yi;Geiger, Hartmut
在衰老期间观察到的造血功能的功能性下降涉及免疫应答的进行性降低和骨髓恶性肿瘤的发病率增加，并且已经与造血干细胞（HSC）的衰老相关联。HSC衰老的分子机制尚不清楚。在这里，我们证明了老年HSC中小RhoGTdCdc42的活性升高与HSC老化有因果关系，并与老年HSC中极性的丧失相关。Cdc42活性的药理学抑制在功能上使老化的HSC恢复活力，增加老化的HSC群体中极化细胞的百分比，并将组蛋白H4赖氨酸16乙酰化的水平和空间分布恢复到与年轻HSC中所见的类似状态。因此，我们的数据表明Cdc42活性在HSC生物学和表观遗传调控中的机械作用，并确定Cdc42活性作为改善干细胞衰老的药理学靶点。
The functional 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 similar status as 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.
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影响因子：
64.5
作者：
Adolfsson, J;Månsson, R;Jacobsen, SEW
通讯作者：
Jacobsen, SEW
DOI：
10.1084/jem.20111490
发表时间：
2011-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dykstra B;Olthof S;Schreuder J;Ritsema M;de Haan G
通讯作者：
de Haan G
影响因子：
64.8
作者：
Janzen, Viktor;Forkert, Randolf;Scadden, David T.
通讯作者：
Scadden, David T.
影响因子：
5.2
作者：
Kamminga, LM;Van Os, R;De Haan, G
通讯作者：
De Haan, G
影响因子：
20.3
作者：
Chung, Yun Shin;Kim, Hye Joung;Oh, Il-Hoan
通讯作者：
Oh, Il-Hoan