PT  - JOURNAL ARTICLE
AU  - Qingran Kong
AU  - Xiaolei Zhang
AU  - Jiaming Zhang
AU  - Kailun Zheng
AU  - Heng Zhang
AU  - Xixiang Pei
AU  - Zhi Yin
AU  - Duancheng Wen
AU  - Zhonghua Liu
TI  - Long noncoding RNAs sustain high expression of exogenous Oct4 by sponging miRNA during reprogramming
AID  - 10.1101/612077
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 612077
4099  - http://biorxiv.org/content/early/2019/04/17/612077.short
4100  - http://biorxiv.org/content/early/2019/04/17/612077.full
AB  - Long noncoding RNAs (lncRNAs) modulate gene expression as competing endogenous RNAs (ceRNAs) via sponging microRNAs (miRNAs). However, the extent and functional consequences of ceRNAs in diverse cellular context still need to be proven. Using a doxycycline inducible expression of Yamanaka four factors to generate induced pluripotent stem cells (iPSCs) from mouse embryonic fibroblasts (MEFs), we found the miRNAs from MEFs remained highly expressed from day 0 to day 6 after doxycycline induction; unexpectedly, many genes targeted by these miRNAs were actually up-regulated; meanwhile, long intergenic noncoding RNAs (lincRNAs) and circular RNAs (circRNAs) which have complementary binding sites with the miRNAs were highly expressed, indicating lincRNAs and circRNAs (linc/circRNAs) may serve as sponges for miRNAs to block their activities during reprogramming. Intriguingly, the knockdown of the linc/circRNAs sponging the miRNAs targeting Oct4 mRNA resulted in down-regulation of exogenous Oct4 expression, decrease of reprogramming efficiency, and low-grade chimera forming iPSCs. Our results suggest that the ceRNA network plays an important role in reprogramming somatic cells to pluripotent stem cells.