Changes in global microRNAome responses to ionizing radiation in human embryonic stem cells implicate cell cycle and cell differentiation regulation

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	CC	STEMCELL-2

Author

• R.D. Neumann

Abstract

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 stress response of human embryonic stem cells (hESC) has not been studied yet. Here, by using systems biology approaches, we show for the first time, that miRNAome undergoes global alterations in hESC (H1 and H9 lines) after IR. Analysis of the expression levels of 1,090 miRNA species in irradiated hESC showed statistically significant changes in 57 genes following 1 Gy of X-ray exposures. Time-course studies demonstrated that the 16 hr-late miRNAome radiation response of hESC is much more robust compared to 2 hr-response signature (only 9 genes); and implicate regulation of the cell cycle and cell differentiation processes in irradiated hESC. We idientified hsa-mir-575 as one of the most overexpressed miRNA species following IR; and here we present evidence of its involvement in regulation of “stemness” 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.

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