Decidual cell polyploidization necessitates mitochondrial activity.
Decidual cell polyploidization necessitates mitochondrial activity.
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DOI：
10.1371/journal.pone.0026774
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Das SK
中科院分区：
文献类型：
--
作者：
Ma X;Gao F;Rusie A;Hemingway J;Ostmann AB;Sroga JM;Jegga AG;Das SK
细胞多倍体在自然界中已被广泛报道，但其发育机制和功能尚不清楚。在本研究中，为了更好地定义卵泡细胞多倍体的各个方面，我们从体内卵泡床中分离了纯多倍体和非多倍体卵泡细胞群体。为每个群体准备三个独立的RNA池，然后对整个小鼠基因组转录物进行Affymetrix基因芯片分析。我们的数据显示，与非多倍体群体相比，多倍体群体中有1015个基因上调，1207个基因下调。对比RT-PCR和原位杂交的结果确实证实了两个群体之间几个基因的差异表达调控。基于功能富集分析，上调的多倍体基因似乎涉及多种功能，主要包括细胞/核分裂、ATP结合、代谢过程和线粒体活性，而下调的基因主要包括细胞凋亡和免疫过程。对线粒体和双核相关基因的进一步分析显示，在个体床内的差异和区域表达与多倍体的模式一致。一致地，研究揭示了多倍体细胞中线粒体质量和ATP产生的显著诱导。各种药物抑制剂以及sirna介导的基因特异性靶向技术对线粒体活性的抑制表明，在体外基质细胞脱倍化过程中，线粒体的多倍体和双核发育显著减弱，这表明线粒体在蜕细胞多倍体化的积极调控中发挥了重要作用。总的来说，分析独特的多倍体标记和分子信号网络可能有助于进一步表征着床部位的蜕细胞多倍体的功能方面。
Cellular polyploidy has been widely reported in nature, yet its developmental mechanism and function remain poorly understood. In the present study, to better define the aspects of decidual cell polyploidy, we isolated pure polyploid and non-polyploid decidual cell populations from the in vivo decidual bed. Three independent RNA pools prepared for each population were then subjected to the Affymetrix gene chip analysis for the whole mouse genome transcripts. Our data revealed up-regulation of 1015 genes and down-regulation of 1207 genes in the polyploid populations, as compared to the non-polyploid group. Comparative RT-PCR and in situ hybridization results indeed confirmed differential expressional regulation of several genes between the two populations. Based on functional enrichment analyses, up-regulated polyploidy genes appeared to implicate several functions, which primarily include cell/nuclear division, ATP binding, metabolic process, and mitochondrial activity, whereas that of down-regulated genes primarily included apoptosis and immune processes. Further analyses of genes that are related to mitochondria and bi-nucleation showed differential and regional expression within the decidual bed, consistent with the pattern of polyploidy. Consistently, studies revealed a marked induction of mitochondrial mass and ATP production in polyploid cells. The inhibition of mitochondrial activity by various pharmacological inhibitors, as well as by gene-specific targeting using siRNA-mediated technology showed a dramatic attenuation of polyploidy and bi-nucleation development during in vitro stromal cell decidualization, suggesting mitochondria play a major role in positive regulation of decidual cell polyploidization. Collectively, analyses of unique polyploidy markers and molecular signaling networks may be useful to further characterize functional aspects of decidual cell polyploidy at the site of implantation.
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