MicroRNAs play important roles in controlling the embryonic stem cell (ESC) state. Although much is known about microRNAs maintaining ESC state, microRNAs that are responsible for promoting ESC differentiation are less reported. Here, by screening 40 microRNAs pre-selected by their expression patterns and predicted targets in Dgcr8-null ESCs, we identify 14 novel differentiation-associated microRNAs. Among them, miR-27a and miR-24, restrained by c-Myc in ESC, exert their roles of silencing self-renewal through directly targeting several important pluripotency-associated factors, such as Oct4, Foxo1 and Smads. CRISPR/Cas9-mediated knockout of all miR-27/24 in ESCs leads to serious deficiency in ESC differentiation in vitro and in vivo. Moreover, depleting of them in mouse embryonic fibroblasts can evidently promote somatic cell reprogramming. Altogether, our findings uncover the essential role of miR-27 and miR-24 in ESC differentiation and also demonstrate novel microRNAs responsible for ESC differentiation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339122 | PMC |
| http://dx.doi.org/10.15252/embj.201489957 | DOI Listing |
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Article Synopsis
- Neurodevelopmental abnormalities contribute to various neurological disorders, with ubiquitination being crucial for embryonic development and neurodevelopment.
- Cnot4, an E3-ubiquitin ligase, was studied for its role in mouse embryonic stem cells (ESCs) where its ubiquitination-deficit led to decreased proliferation and increased ectodermal differentiation.
- RNA sequencing revealed that genes linked to glucose metabolism and calcium signaling were affected, indicating Cnot4's significant role in regulating ESC behavior through ubiquitination.
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