Characterization of Cell Cycle Phase-Based Micrornas in Pluripotency and Differentiation
Xiao Qi Wang*, Xiaoyan Ming, Timothy Ming-Hun Wan, Lin Chen, Maria Mercedes Garcia-Barcelo and Chung Mau Lo
Department of Surgery, The University of Hong Kong, Hong Kong, China
- *Corresponding Author:
- Xiao Qi Wang, D.Phil.
Department of Surgery, The University of Hong Kong
21 Sassoon Road, Hong Kong
E-mail: [email protected]
Received date: December 31, 2016; Accepted date: January 18, 2017; Published date: January 25, 2017
Citation: Wang XQ, Ming X, Ming-Hun Wan T, Chen L, Garcia-Barcelo MM, et al. (2017) Characterization of Cell Cycle Phase-Based microRNAs in Pluripotency and Differentiation. Cell Dev Biol 6:178. doi:10.4172/2168-9296.1000178
Copyright: © 2017 Wang XQ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
In addition to signaling pathways, transcription factors and epigenetic regulators, microRNAs (miRNAs) are emerging as important regulators of human pluripotent stem cells (hPSCs). Pluripotent miRNAs that regulate G1-S transition and pluripotency factors to maintain self-renewal have been identified. However, only 4-5 clusters of miRNAs have been identified in human embryonic stem cells (hESCs). We performed cell cycle phase-based (G1, S, and G2/M phases) miRNA array in pluripotent and differentiated hESCs. We demonstrated that embryonic stem cell-cell cycle (ESCC) regulating miRNAs were all highly expressed in three cell cycle phases of undifferentiated hESCs suggesting a non-cell phase regulated mechanism. From cell phase-dependent miRNAs, G2/M-miRNAs was extracted by principle component analysis (PCA) as a significant component in pluripotent hESCs, whereas G1-miRNAs was a significant component in differentiated hESCs. The results indicate that G2/M-miRNAs might function to maintain pluripotency and G1-miRNAs might function to enhance differentiation. By miRNA target site prediction, G2/M-phase miRNA displayed potential target sites on differentiation factors GATA6 and GATA4, G1-phase miRNAs displayed potential target sites on pluripotency gene OCT4, NANOG, and SOX2, which warrant further confirmation and functional study. By statistical and computation analysis of the miRNA array data, we demonstrated that the G2/M-miRNAs could potentially repress differentiation factors to maintain pluripotency, and G1-miRNAs could potentially target pluripotency genes to enhance differentiation.