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IMR32 神经母细胞瘤的分化伴随着转录组的全局变化。

Differentiation of IMR32 Neuroblastoma Is Accompanied by a Global Change in the Transcriptome.

机构信息

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

出版信息

Dokl Biochem Biophys. 2021 Mar;497(1):90-94. doi: 10.1134/S1607672921020149. Epub 2021 Apr 24.

Abstract

Neuroblastoma is one of the most common cancers in infants and is often multidrug-resistant. One of the methods of treating neuroblastomas is to create conditions for their differentiation. In this work, we performed a full-transcriptome analysis of gene expression in an undifferentiated and differentiated in vitro human neuroblastoma cell line IMR-32 and identified the signaling pathways and biological processes that undergo the greatest changes during differentiation. The results obtained show that a complex heterogeneous population of nerve cells is formed at different stages of differentiation. In the cell population of differentiating neuroblastoma, the expression of genes in which cortical neuronal progenitor cells are enriched increases; at the same time, there are cells expressing markers of early postmitotic neurons. Cells differentiate in several different directions according to the type of synaptic mediator. At the same time, the differentiation of IMR-32 cells is accompanied by an increase in the transcription of genes that suppress the differentiation of nerve cells, Sox2 and PROM1, the expression of which is normally suppressed during in vivo differentiation.

摘要

神经母细胞瘤是婴儿中最常见的癌症之一,且经常对多种药物具有抗药性。治疗神经母细胞瘤的方法之一是为其分化创造条件。在这项工作中,我们对未分化和体外分化的人类神经母细胞瘤细胞系 IMR-32 进行了全转录组基因表达分析,并确定了在分化过程中发生最大变化的信号通路和生物学过程。结果表明,在不同的分化阶段形成了一个复杂的异质神经元细胞群体。在分化的神经母细胞瘤细胞群体中,富含皮质神经元祖细胞的基因表达增加;同时,也有表达早期有丝分裂后神经元标记物的细胞。根据突触介质的类型,细胞向不同的方向分化。同时,IMR-32 细胞的分化伴随着抑制神经细胞分化的基因转录增加,Sox2 和 PROM1 的转录增加,它们在体内分化过程中通常受到抑制。

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