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小鼠多能干细胞和畸胎癌细胞自我更新与分化过程中家族基因的表达动态

Expression dynamics of family genes during self-renewal and differentiation of mouse pluripotent stem and teratocarcinoma cells.

作者信息

Gordeeva Olga, Gordeev Andrey, Khaydukov Sergey

机构信息

Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.

National Institutes of Health's National Library of Medicine, Bethesda, MD, USA.

出版信息

Oncotarget. 2019 May 14;10(35):3248-3266. doi: 10.18632/oncotarget.26933.

Abstract

The biological roles of cancer-testis antigens of the Melanoma antigen (Mage) family in mammalian development, stem cell differentiation and carcinogenesis are largely unknown. In order to understand the involvement of the family genes in maintenance of normal and cancer stem cells, the expression patterns of and gene subfamilies were analyzed during the self-renewal and differentiation of mouse pluripotent stem and teratocarcinoma cells. Clustering analysis based on the gene expression profiles of undifferentiated and differentiating cell populations revealed strong correlations between expression patterns and differentiation and malignant states. Gene co-expression analysis disclosed the potential contributions of family members in self-renewal and differentiation of pluripotent stem and teratocarcinoma cells. Two gene clusters including and were identified as functional antagonists with opposing roles in the regulation of proliferation and differentiation of mouse pluripotent stem and teratocarcinoma cells. The identified aberrant expression patterns of and in teratocarcinoma cells can be considered as specific teratocarcinoma biomarkers promoted the malignant phenotype. Our study first provides a model for the involvement of family members in regulatory networks during the self-renewal and early differentiation of normal and cancerous stem cells for further research of the predicted functional modules and the development of new cancer treatment strategies.

摘要

黑色素瘤抗原(Mage)家族的癌睾丸抗原在哺乳动物发育、干细胞分化和致癌过程中的生物学作用在很大程度上尚不清楚。为了了解该家族基因在正常和癌症干细胞维持中的作用,我们分析了小鼠多能干细胞和畸胎癌细胞自我更新和分化过程中 和 基因亚家族的表达模式。基于未分化和分化细胞群体基因表达谱的聚类分析揭示了 表达模式与分化及恶性状态之间的强相关性。基因共表达分析揭示了 家族成员在多能干细胞和畸胎癌细胞自我更新和分化中的潜在作用。两个基因簇,包括 和 ,被鉴定为在小鼠多能干细胞和畸胎癌细胞增殖和分化调节中具有相反作用的功能拮抗剂。在畸胎癌细胞中鉴定出的 和 的异常表达模式可被视为促进恶性表型的特异性畸胎癌生物标志物。我们的研究首次为 家族成员参与正常和癌性干细胞自我更新和早期分化过程中的调控网络提供了一个模型,以便进一步研究预测的功能模块并开发新的癌症治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e576/6524934/0c2af6160d41/oncotarget-10-3248-g001.jpg

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