Embryonic Stem Cell Specific MicroRNAs Regulate the G1/S Transition and Promote Rapid Proliferation

By Yangming Wang, S. Baskerville, Archana Shenoy, Joshua Babiarz, L. Baehner, Robert Blelloch. Nature Genetics, 2008

677 citations recorded by the source corpus.

Dgcr8 knockout embryonic stem (ES) cells lack microprocessor activity and hence all canonical microRNAs (miRNAs). These cells proliferate slowly and accumulate in G1 phase of the cell cycle. Here, by screening a comprehensive library of individual miRNAs in the background of the Dgcr8 knockout ES cells, we report that multiple ES cell–specific miRNAs, members of the miR-290 family, rescue the ES cell proliferation defect. Furthermore, rescued cells no longer accumulate in the G1 phase of the cell cycle. These miRNAs function by suppressing several key regulators of the G1-S transition. These results show that post-transcriptional regulation by miRNAs promotes the G1-S transition of the ES cell cycle, enabling rapid proliferation of these cells. Our screening strategy provides an alternative and powerful approach for uncovering the role of individual miRNAs in biological processes, as it overcomes the common problem of redundancy and saturation in the miRNA system.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6ed4583ffee90701dd927268f0f1f488534a230a

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Citations in the corpus

Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency (2011, neutral): “These miRNAs belong to families of miRNAs that are expressed preferentially in embryonic stem cells and are thought to help maintain the ESC phenotype (Babiarz et al., 2008; Wang et al., 2007, 2008; Wang and Blelloch, 2009;).”
Control of Embryonic Stem Cell State (2011, background): “…cluster, and miRNAs with seed sequences in this family have been implicated in cell proliferation (He et al., 2005; O’Donnell et al., 2005; Wang et al., 2008) and have been shown to rescue the proliferation defects observed in miRNA-deficient ES cells (Kanellopoulou et al., 2005;…”
Non-coding RNAs as regulators of embryogenesis (2011, background): “The proliferation defects of Dgcr8 mutant mouse ES cells are partially rescued by expression of mature members of the miR-290–295/302 famil”
Senescence impairs successful reprogramming to pluripotent stem cells. (2009, background): “It has been suggested that these ES cell-specific miRNAs are necessary for the normal proliferation of ES cells, and function by targeting negative cell cycle regulators such as p21Cip1, the RB homolog p130, or LATS2 (Wang et al., 2008).”
Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease (2019, background): “On the other hand, some cells, like adipocytes and stem cells, express a wide range of miRNAs (Houbaviy et al., 2003; Kim et al., 2014; Kloting et al., 2009; Marson et al., 2008; Mori et al., 2012; Wang et al., 2008; Xie et al., 2009).”