Prediction of hub genes and key pathways associated with the radiation response of human hematopoietic stem/progenitor cells using integrated bioinformatics methods

被引:3
作者
Sato, Yoshiaki [1 ]
Yoshino, Hironori [1 ]
Ishikawa, Junya [2 ]
Monzen, Satoru [1 ]
Yamaguchi, Masaru [1 ]
Kashiwakura, Ikuo [1 ]
机构
[1] Hirosaki Univ, Grad Sch Hlth Sci, Dept Radiat Sci, Hirosaki, Aomori 0368564, Japan
[2] Kyorin Univ, Fac Hlth Sci, Dept Med Radiol Technol, Mitaka, Tokyo 1818612, Japan
基金
日本学术振兴会;
关键词
DNA-DAMAGE; EXPRESSION; RADIOSENSITIVITY; REGENERATION; MAINTENANCE; ANTICANCER; ACTIVATION; CYTOSCAPE; PROMOTE; STRESS;
D O I
10.1038/s41598-023-37981-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hematopoietic stem cells (HSCs) are indispensable for the maintenance of the entire blood program through cytokine response. However, HSCs have high radiosensitivity, which is often a problem during radiation therapy and nuclear accidents. Although our previous study has reported that the combination cytokine treatment (interleukin-3, stem cell factor, and thrombopoietin) improves the survival of human hematopoietic stem/progenitor cells (HSPCs) after radiation, the mechanism by which cytokines contribute to the survival of HSPCs is largely unclear. To address this issue, the present study characterized the effect of cytokines on the radiation-induced gene expression profile of human CD34(+) HSPCs and explored the hub genes that play key pathways associated with the radiation response using a cDNA microarray, a protein-protein interaction-MCODE module analysis and Cytohubba plugin tool in Cytoscape. This study identified 2,733 differentially expressed genes (DEGs) and five hub genes (TOP2A, EZH2, HSPA8, GART, HDAC1) in response to radiation in only the presence of cytokines. Furthermore, functional enrichment analysis found that hub genes and top DEGs based on fold change were enriched in the chromosome organization and organelle organization. The present findings may help predict the radiation response and improve our understanding of this response of human HSPCs.
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页数:11
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