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Temporal Control of the TGF-β Signaling Network by Mouse ESC MicroRNA Targets of Different Affinities

Cell Rep. 2019; 
Kelly TJ, Brümmer A, Hooshdaran N, Tariveranmoshabad M, Zamudio JR
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摘要

Although microRNAs (miRNAs) function in the control of embryonic stem cell (ESC) pluripotency, a systems-level understanding is still being developed. Through the analysis of progressive Argonaute (Ago)-miRNA depletion and rescue, including stable Ago knockout mouse ESCs, we uncover transforming growth factor beta (TGF-β) pathway activation as a direct and early response to ESC miRNA reduction. Mechanistically, we link the derepression of weaker miRNA targets, including TGF-β receptor 1 (Tgfbr1), to the sensitive TGF-β pathway activation. In contrast, stronger miRNA targets impart a more robust repression, which dampens concurrent transcriptional activation. We verify such dampened induction for TGF-β antag... More

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