Continual Expression Throughout the Cell Cycle and Downregulation upon Adipogenic Differentiation Makes Nucleostemin a Vital Human MSC Proliferation Marker

Continual Expression Throughout the Cell Cycle and Downregulation upon Adipogenic Differentiation Makes Nucleostemin a Vital Human MSC Proliferation Marker
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在整个细胞周期中持续表达和成脂分化时的下调使 Nucleostemin 成为重要的人类 MSC 增殖标志物

DOI:
10.1007/s12015-010-9201-y
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发表时间:
2011
影响因子:
4.8
通讯作者:
A. Can
A. Can
中科院分区:
医学3区
文献类型:
--
作者:
P. Oktar;S. Yıldırım;D. Balcı;A. Can

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核干细胞蛋白(NS)是一种在干细胞和癌细胞中表达的核仁蛋白。与核/核仁蛋白结合,NS已被证明参与细胞周期调节和端粒维持。NS表达反映了细胞的增殖状态,表明细胞在细胞周期中是活跃的,而NS信号在分化时消失。本研究分析了时空(核仁/核定位在间期和M期)NS重塑在两个不同的人间充质干细胞(MSC)群体的歧视NS的差异,如果有的话,在整个干细胞和分化状态。除了其突出的多小叶核仁定位在间期细胞,NS与染色体臂在有丝分裂过程中的共存也被观察到。有丝分裂微管的破坏诱导NS从染色体臂上解离,并将其分散到细胞质中。与乳牙牙髓间充质干细胞相比,随着培养时间的延长,脐带间充质干细胞中NS mRNA的表达逐渐降低。后者的成脂分化后,NS信号逐渐消失在分裂和非分裂细胞,甚至在成脂转化的形态和功能迹象出现之前。定量NS mRNA的测量结果表明,从两个来源的MSC表现出强烈的核干细胞的表达类似于胚胎干细胞。总之,除了其新的染色体定位显示在这项研究中,核仁NS可以被认为是一个标志物,表明在人类骨髓间充质干细胞的增殖/分化状态。此外,相对NS蛋白和mRNA水平的差异可反映增殖的程度,并可用于表征体外扩增能力。
Nucleostemin (NS) is a nucleolar protein expressed in stem and cancer cells. In combination with nuclear/nucleolar proteins, NS has been demonstrated to be involved in cell-cycle regulation and telomere maintenance. NS expression reflects the cell’s proliferation state indicating that the cell is active in the cell cycle, whereas NS signals disappear upon differentiation. This study analyzes the spatio-temporal (nucleolar/nuclear localization during interphase and M-phase) NS remodeling in two distinct human mesenchymal stem cell (MSC) populations to discriminate the NS differences, if any, throughout their stem cell and differentiation states. Beside its prominent multilobular nucleolar localization in interphase cells, coexistence of NS with chromosome arms during mitosis was also observed. Disruption of mitotic microtubules induced dissociation of NS from the chromosome arms and scattered it into the cytoplasm. Compared to deciduous dental pulp MSCs, NS mRNA expression gradually decreased upon aging in umbilical cord stroma-derived MSCs as culture time increased. Following adipogenic differentiation of the latter, NS signals gradually disappeared in both dividing and non-dividing cells, even before the morphological and functional signs of adipogenic transformation appeared. Quantitative NS mRNA measurements showed that MSCs from two sources exhibit a strong nucleostemin expression similar to embryonic stem cells. In conclusion, apart from its novel chromosomal localization shown in this study, nucleolar NS can be considered as a marker that indicates the proliferation/differentiation states in human MSCs. Moreover, differences in the relative NS protein and mRNA levels may reflect the degree of proliferation and can be used to characterize in vitro expansion capabilities.
DOI: 10.1101/gad.55671
发表时间: 2002-12-01
影响因子: 10.5
作者:
Tsai, RYL;McKay, RDG
通讯作者: McKay, RDG
DOI: 10.1016/j.bbrc.2009.04.077
发表时间: 2009-06-19
影响因子: 3.1
作者:
Li N;Yuan K;Yan F;Huo Y;Zhu T;Liu X;Guo Z;Yao X
通讯作者: Yao X