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Tuesday, October 25, 2011 — Poster Session II | |||
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Noon – 2:00 p.m. |
Natcher Conference Center |
CC |
STEMCELL-6 |
MicroRNAs (miRNA) comprise a group of short ribonucleic acid molecules implicated in regulation of key biological processes and functions at the post-transcriptional level. Ionizing radiation (IR) causes DNA damage and generally triggers cellular stress response. However, the role of miRNAs in DNA damage response (DDR) in human embryonic stem cells (hESC) has not been defined yet. Here, by using system biology approaches, we show for the first time, that miRNAome undergoes global alterations in hESC (H1 and H9 lines) after IR. Interrogation of expression levels of 1,090 miRNA species in irradiated hESC showed statistically significant changes in 57 genes following one Gy of X-ray exposures. Time-course studies showed that the 16 hr-late miRNAome radiation response of hESC is much more robust compared to two hr-response signature (only nine genes), and may be involved in regulating the cell cycle in irradiated hESC. We identified miRNA-based radiation exposure-related gene expression signature that can predict the status of hESC. Positive regulation of differentiation-, ion transport- and endomembrane system-related processes were found to be negatively affected by miRNAome changes in irradiated hESC. Our findings reveal a fundamental role of miRNAome in modulating the radiation response, and identify novel molecular targets of radiation in hESC.