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Transcriptomes reflect the phenotypes of undifferentiated, granulocyte and macrophage forms of HL-60/S4 cells

机译:转录组反映了未分化的HL-60 / S4细胞的粒细胞和巨噬细胞形式的表型

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To understand the chromatin changes underlying differential gene expression during induced differentiation of human leukemic HL-60/S4 cells, we conducted RNA-Seq analysis on quadruplicate cultures of undifferentiated, granulocytic- and macrophage-differentiated cell forms. More than half of mapped genes exhibited altered transcript levels in the differentiated cell forms. In general, more genes showed increased mRNA levels in the granulocytic form and in the macrophage form, than showed decreased levels. The majority of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in genes that exhibited differential transcript levels after either RA or TPA treatment. Changes in transcript levels for groups of genes with characteristic protein phenotypes, such as genes encoding cytoplasmic granular proteins, nuclear envelope and cytoskeletal proteins, cell adhesion proteins, and proteins involved in the cell cycle and apoptosis illustrate the profound differences among the various cell states. In addition to the transcriptome analyses, companion karyotyping by M-FISH of undifferentiated HL-60/S4 cells revealed a plethora of chromosome alterations, compared with normal human cells. The present mRNA profiling provides important information related to nuclear shape changes (e.g., granulocyte lobulation), deformability of the nuclear envelope and linkage between the nuclear envelope and cytoskeleton during induced myeloid chromatin differentiation.
机译:为了了解在人类白血病HL-60 / S4细胞诱导分化过程中差异基因表达背后的染色质变化,我们对未分化,粒细胞和巨噬细胞分化细胞形式的一式四份培养物进行了RNA-Seq分析。超过一半的作图基因在分化的细胞形式中表现出改变的转录水平。通常,更多的基因显示出颗粒细胞形式和巨噬细胞形式的mRNA水平增加,而不是水平下降。在《京都议定书》中,大多数基因和基因组百科全书(KEGG)途径均显着富集了在RA或TPA处理后表现出不同转录水平的基因。具有特征蛋白表型的基因组的转录水平的变化,例如编码胞质颗粒蛋白,核被膜和细胞骨架蛋白,细胞粘附蛋白以及参与细胞周期和凋亡的蛋白的基因,说明了各种细胞状态之间的深刻差异。除转录组分析外,与未分化的HL-60 / S4细胞相比,未分化的HL-60 / S4细胞通过M-FISH进行的伴随核型分析显示,与正常人细胞相比,存在过多的染色体改变。本发明的mRNA谱提供了与核形状改变(例如粒细胞小叶化),核被膜的可变形性以及在诱导的髓系染色质分化过程中核被膜与细胞骨架之间的联系有关的重要信息。

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