TY - JOUR
T1 - Expression analysis of radiation-responsive genes in human hematopoietic stem/progenitor cells
AU - Tsujiguchi, Takakiyo
AU - Hirouchi, Tokuhisa
AU - Monzen, Satoru
AU - Tabuchi, Yoshiaki
AU - Takasaki, Ichiro
AU - Kondo, Takashi
AU - Kashiwakura, Ikuo
N1 - Publisher Copyright:
© 2015 The Author 2015.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - Gene expression
KW - Hematopoietic stem and progenitor cells
KW - Radiosensitivity
KW - Umbilical cord blood
UR - http://www.scopus.com/inward/record.url?scp=84959873301&partnerID=8YFLogxK
U2 - 10.1093/jrr/rrv071
DO - 10.1093/jrr/rrv071
M3 - 学術論文
C2 - 26661850
AN - SCOPUS:84959873301
SN - 0449-3060
VL - 57
SP - 35
EP - 43
JO - Journal of Radiation Research
JF - Journal of Radiation Research
IS - 1
ER -