Long noncoding RNAs sustain high expression of exogenous Oct4 by sponging miRNA during reprogramming
Long noncoding RNAs sustain high expression of exogenous Oct4 by sponging miRNA during reprogramming
Abstract 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.
Zhang Jiaming、Zheng Kailun、Pei Xixiang、Wen Duancheng、Liu Zhonghua、Kong Qingran、Zhang Xiaolei、Zhang Heng、Yin Zhi
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural UniversityKey Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural UniversityHarbin Botai Bio-Tech Co., Ltd.Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical CollegeKey Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural UniversityKey Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University||Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical CollegeKey Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural UniversityKey Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural UniversityKey Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University
分子生物学遗传学细胞生物学
ceRNAscircRNAslincRNAsmiRNAsreprogramming
Zhang Jiaming,Zheng Kailun,Pei Xixiang,Wen Duancheng,Liu Zhonghua,Kong Qingran,Zhang Xiaolei,Zhang Heng,Yin Zhi.Long noncoding RNAs sustain high expression of exogenous Oct4 by sponging miRNA during reprogramming[EB/OL].(2025-03-28)[2025-04-27].https://www.biorxiv.org/content/10.1101/612077.点此复制
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