Expression Analysis of Radiation-responsive Genes in Human Hematopoietic Stem/progenitor Cells

Overview

Journal J Radiat Res

Publisher Oxford University Press

Specialties Environmental Health
Oncology
Radiology

Date 2015 Dec 15

PMID 26661850

Citations 3

Authors

Takakiyo Tsujiguchi

Tokuhisa Hirouchi

Satoru Monzen

Yoshiaki Tabuchi

Ichiro Takasaki

Takashi Kondo

Ikuo Kashiwakura

Affiliations

Soon will be listed here.

Abstract

To clarify the nature of the genes that contribute to the radiosensitivity of human hematopoietic stem/progenitor cells (HSPCs), we analyzed the gene expression profiles detected in HSPCs irradiated with 2 Gy X-rays after culture with or without an optimal combination of hematopoietic cytokines. Highly purified CD34(+) cells from human placental/umbilical cord blood were used as HSPCs. The cells were exposed to 2 Gy X-irradiation and treated in serum-free medium under five different sets of conditions for 6 h. The gene expression levels were analyzed by cDNA microarray, and then the network of responsive genes was investigated. A comprehensive genetic analysis to search for genes associated with cellular radiosensitivity was undertaken, and we found that expression of the genes downstream of MYC oncogene increased after X-irradiation. In fact, the activation of MYC was observed immediately after X-irradiation, and MYC was the only gene still showing activation at 6 h after irradiation. Furthermore, MYC had a significant impact on the biological response, particularly on the tumorigenesis of cells and the cell cycle control. The activated gene regulator function of MYC resulting from irradiation was suppressed by culturing the HSPCs with combinations of cytokines (recombinant human thrombopoietin + interleukin 3 + stem cell factor), which exerted radioprotective effects. MYC was strongly associated with the radiosensitivity of HSPCs, and further study and clarification of the genetic mechanisms that control the cell cycle following X-irradiation are required.

Citing Articles

Ferroptosis, Inflammation, and Microbiome Alterations in the Intestine in the Göttingen Minipig Model of Hematopoietic-Acute Radiation Syndrome.

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

Sato Y, Yoshino H, Ishikawa J, Monzen S, Yamaguchi M, Kashiwakura I Sci Rep. 2023; 13(1):10762.

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MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation.

Gupta P, Gayen M, Smith J, Gaidamakova E, Matrosova V, Grichenko O PLoS One. 2016; 11(8):e0160575.

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