Senescence-Associated Molecular and Epigenetic Alterations in Mesenchymal Stem Cell Cultures from Amniotic Fluid of Normal and Fetus-Affected Pregnancy.
Senescence-Associated Molecular and Epigenetic Alterations in Mesenchymal Stem Cell Cultures from Amniotic Fluid of Normal and Fetus-Affected Pregnancy.
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DOI：
10.1155/2016/2019498
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发表时间：
2016
影响因子：
4.3
通讯作者：
Navakauskienė R
中科院分区：
文献类型：
--
作者：
Savickienė J;Baronaitė S;Zentelytė A;Treigytė G;Navakauskienė R
人骨髓间充质干细胞（AF-MSCs）因其多向分化潜能和广泛的治疗应用而引起人们的兴趣，这是由于易于培养扩增。然而，MSC经历复制性衰老。到目前为止，胎儿疾病和细胞衰老的分子机制仍然知之甚少。在这里，我们分析了衰老相关的形态学，分子和表观遗传学特征，在增殖过程中的间充质干细胞来自AF的正常和胎儿影响的怀孕。来自两种细胞来源的AF-MSCs培养物显示出非常相似的形态学和特异性细胞表面（CD 44、CD 90和CD 105）和干性（Oct 4、Nanog、Sox 2和Rex 1）标志物的表达，但在增殖能力和达到衰老的时间方面存在个体间差异。在第4代和第8代内，衰老培养物表现出典型的形态学特征、衰老相关的β-半乳糖苷酶活性、p16水平升高以及miR-17和miR-21水平降低，但表现出依赖于细胞衰老开始的p21、p53和ATM的差异表达。这些差异与染色质修饰剂（DNMT 1和HDAC 1）和polycomb组蛋白（EZH 2，SUZ 12和BMI 1）水平的变化相关，与抑制性组蛋白标记（H3 K9 me 3和H3 K27 me 3）和干性标记（Oct 4，Nanog，Sox 2和Rex 1）表达的变化平行。因此，表观遗传因素在AF-MSCs衰老过程中起重要作用，可能与供体个体或胎儿恶性肿瘤状态有关。
Human amniotic-fluid-derived mesenchymal stem cells (AF-MSCs) are interesting for their multilineage differentiation potential and wide range of therapeutic applications due to the ease of culture expansion. However, MSCs undergo replicative senescence. So far, the molecular mechanisms that underlie fetal diseases and cell senescence are still poorly understood. Here, we analyzed senescence-associated morphologic, molecular, and epigenetic characteristics during propagation of MSCs derived from AF of normal and fetus-affected pregnancy. AF-MSCs cultures from both cell sources displayed quite similar morphology and expression of specific cell surface (CD44, CD90, and CD105) and stemness (Oct4, Nanog, Sox2, and Rex1) markers but had interindividual variability in proliferation capability and time to reach senescence. Within passages 4 and 8, senescent cultures exhibited typical morphological features, senescence-associated β-galactosidase activity, increased levels of p16, and decreased levels of miR-17 and miR-21 but showed differential expression of p21, p53, and ATM dependently on the onset of cell senescence. These differences correlated with changes in the level of chromatin modifiers (DNMT1 and HDAC1) and polycomb group proteins (EZH2, SUZ12, and BMI1) paralleling with changes in the expression of repressive histone marks (H3K9me3 and H3K27me3) and stemness markers (Oct4, Nanog, Sox2, and Rex1). Therefore epigenetic factors are important for AF-MSCs senescence process that may be related with individuality of donor or a fetus malignancy status.
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影响因子：
4.5
作者：
Grillari, Johannes;Hackl, Matthias;Grillari-Voglauer, Regina
通讯作者：
Grillari-Voglauer, Regina
复制性衰老与特定转录因子结合位点处的核重组和DNA甲基化有关。
影响因子：
5.7
作者：
Hänzelmann S;Beier F;Gusmao EG;Koch CM;Hummel S;Charapitsa I;Joussen S;Benes V;Brümmendorf TH;Reid G;Costa IG;Wagner W
通讯作者：
Wagner W
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：
4
作者：
Izadpanah, Reza;Trygg, Cynthia;Bunnell, Bruce A.
通讯作者：
Bunnell, Bruce A.
影响因子：
3.7
作者：
Maguire CT;Demarest BL;Hill JT;Palmer JD;Brothman AR;Yost HJ;Condic ML
通讯作者：
Condic ML