期刊
STEM CELLS
卷 38, 期 3, 页码 340-351出版社
OXFORD UNIV PRESS
DOI: 10.1002/stem.3130
关键词
differentiation initiation; ESCs; Linc1557; mRNA stability; STAT3
资金
- Ministry of Science and Technology of the People's Republic of China [2016YFA0101300]
- National Natural Science Foundation of China [31571519, 31830059, 31871298, 81530042]
Embryonic stem cells (ESCs) have self-renewal and multi-lineage differentiation potential and perform critical functions in development and biomedicine. Several long noncoding RNAs (lncRNAs) have been reported as key regulators of stem cell pluripotency and differentiation. However, the function and regulatory mechanism of lncRNAs during the initiation of ESC differentiation remains unclear. Here, we found that linc1557 was highly expressed in mouse ESCs and required for the initiation of ESC differentiation. Knockdown of linc1557 increased the expression and phosphorylation levels of signal transducer and activator of transcription 3 (STAT3), a key factor in the leukemia inhibitory factor (LIF)/STAT3 signaling pathway. Furthermore, we found that linc1557 directly bound to Stat3 mRNA and affected its stability. The differentially expressed transcriptome after linc1557 knockdown in ESCs was involved primarily in multicellular organism development and cell differentiation as similar to that after Stat3 knockdown. Moreover, either knockdown of Stat3 or addition of a LIF/STAT3 signaling inhibitor rescued the suppressive effects of linc1557 knockdown on the initiation of mouse ESC differentiation. These findings not only elucidated the critical function of linc1557 in the initiation of mouse ESC differentiation but also clarified that its specific mechanism as directly affecting Stat3 mRNA stability, which enhanced the understanding of the lncRNA-mediated regulatory mechanism for mRNA stability and key signaling pathways in ESC pluripotency and differentiation.
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