5月4日,，國際期刊Cell Stem Cell發(fā)表了德國烏爾姆大學(xué)、美國辛辛那提兒童醫(yī)院醫(yī)學(xué)中心和辛辛那提大學(xué)等處科學(xué)家合作研究的發(fā)現(xiàn),，Cdc42的活性可調(diào)節(jié)造血干細胞（HSC,，hematopoietic stem cells）的衰老和活力。
然而此前,，科學(xué)家普遍認(rèn)為造血干細胞的衰老由細胞內(nèi)部某種機制控制,，無法通過治療干預(yù)扭轉(zhuǎn)。
在衰老過程中,，造血功能隨之下降,，免疫反應(yīng)也逐漸減弱，而骨髓瘤的發(fā)生率上升,。造血干細胞衰老的分子機制尚不清楚,。研究人員發(fā)現(xiàn)，提高造血干細胞中小RhoGTPase Cdc42的活力可促進造血干細胞的衰老,，且衰老的造血干細胞失去極性,。
若采用藥物抑制Cdc42的活性，衰老的造血干細胞活力重新恢復(fù),，極性造血干細胞所占總衰老造血干細胞的比例也增加,。同時，組蛋白H4的16位賴氨酸乙?；揭不謴?fù)到年輕造血干細胞的水平,。
GWAS結(jié)果也表明Cdc42在人白細胞中的表達量與發(fā)病和衰老呈正相關(guān)。衰老小鼠的多種組織中也發(fā)現(xiàn)Cdc42的活性增高,。
可見,，Cdc42在造血干細胞的表觀調(diào)節(jié)中發(fā)揮重要作用，它可作為緩解造血干細胞衰老的藥物靶點,。（生物谷Bioon.com）
doi:10.1016/j.stem.2012.04.007
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PMID:
Cdc42 Activity Regulates Hematopoietic Stem Cell Aging and Rejuvenation
Maria Carolina Florian1, Karin D?rr1, Anja Niebel1, Deidre Daria1, Hubert Schrezenmeier2, Markus Rojewski2, Marie-Dominique Filippi3, Anja Hasenberg4, Matthias Gunzer4, Karin Scharffetter-Kochanek1, Yi Zheng3, Hartmut Geiger
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.
