期刊
STEM CELLS
卷 36, 期 3, 页码 325-336出版社
OXFORD UNIV PRESS
DOI: 10.1002/stem.2749
关键词
Stem cells; Neural differentiation; lncRNA-1604; miR-200c; ZEB
资金
- Ministry of Science and Technology of the People's Republic of China [2016YFA0101300]
- National Natural Science Foundation of China [31371510, 31571519, 31471250, 81530042, 31210103905, 31571529, 31571390]
- Science and Technology Commission of Shanghai Municipality [15JC1403201]
- Fundamental Research Funds for the Central Universities [2000219136, 1500219106]
Clarifying the regulatory mechanisms of embryonic stem cell (ESC) neural differentiation is helpful not only for understanding neural development but also for obtaining high-quality neural progenitor cells required by stem cell therapy of neurodegenerative diseases. Here, we found that long noncoding RNA 1604 (lncRNA-1604) was highly expressed in cytoplasm during neural differentiation, and knockdown of lncRNA-1604 significantly repressed neural differentiation of mouse ESCs both in vitro and in vivo. Bioinformatics prediction and mechanistic analysis revealed that lncRNA-1604 functioned as a novel competing endogenous RNA of miR-200c and regulated the core transcription factors ZEB1 and ZEB2 during neural differentiation. Furthermore, we also demonstrated the critical role of miR-200c and ZEB1/2 in mouse neural differentiation. Either introduction of miR-200c sponge or overexpression of ZEB1/2 significantly reversed the lncRNA-1604 knockdown-induced repression of mouse ESC neural differentiation. Collectively, these findings not only identified a previously unknown role of lncRNA-1604 and ZEB1/2 but also elucidated a new regulatory lncRNA-1604/miR-200c/ZEB axis in neural differentiation.
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