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.

中文翻译：

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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

摘要

神经母细胞瘤是婴儿最常见的癌症之一，通常具有多重耐药性。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，我们对未分化和分化的体外人神经母细胞瘤细胞系 IMR-32 中的基因表达进行了全转录组分析，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。获得的结果表明，在分化的不同阶段形成了复杂的异质神经细胞群。在分化神经母细胞瘤的细胞群中，皮质神经元祖细胞富集的基因表达增加；同时，还有表达早期有丝分裂后神经元标志物的细胞。根据突触介质的类型，细胞在几个不同的方向上分化。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，其表达通常在体内分化过程中受到抑制。