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

机译:转录om反映了无差异化,粒细胞和巨噬细胞形式的HL-60 / S4细胞的表型

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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:为了了解染色质变化在人白血病HL-60 / S4细胞的诱导分化期间差异差异基因表达,我们对未分化的,粒细胞和巨噬细胞和巨噬细胞形式的四份培养进行了RNA-SEQ分析。超过一半的映射基因在分化的细胞形式中表现出改变的转录物水平。通常,更多基因显示出粒细胞形式和巨噬细胞形式的mRNA水平增加,而不是显示出降低水平。基因和基因组(Kegg)途径的大部分京都百科全书(Kegg)途径显着富集,在RA或TPA治疗后表现出差异转录物水平。具有特征蛋白质表型的基因组的转录水平的变化,例如编码细胞质颗粒蛋白,核包封和细胞骨架蛋白,细胞粘附蛋白和涉及细胞周期和细胞凋亡的蛋白质的基因说明了各种细胞状态的深刻差异。除了转录组分析之外,与正常人体细胞相比,由未分化的HL-60 / S4细胞的M-Fish的伴核蛋白酶术语显示出过多的染色体改变。本发明的mRNA分析提供了与核形状变化(例如,粒细胞裂解),核包膜的可变形性以及核包膜和细胞骨架之间的可变形性以及在诱导的骨髓染色质分化期间与核包膜和细胞骨架之间的相关性。

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