Micro vs. micro
The paper:
C. Melton et al., “Opposing microRNA families regulate self-renewal in mouse embryonic stem cells,” Nature, 463:621–26, 2010. (ID: 1899956)
The finding:
In 2007, when Robert Blelloch from the University of California, San Francisco knocked out most microRNAs in embryonic stem (ES) cells, he noticed that the cells could no longer silence self-renewal, suggesting that microRNAs were involved in the process (Nat Genet, 39:380–85, 2007). So Blelloch looked for a microRNA that blocked ES cell self-renewal, a necessary first step in differentiation. They found that two families of microRNAs counteract each other to determine ES cell fate.
The surprise:
Other researchers had shown that the let-7 microRNA family was upregulated in differentiating cells, so Blelloch and colleagues reinserted that microRNA into self-renewing ES cells, blocking the knockout’s ability to self-renew. They then added an microRNA...
The twist:
Using microRNA microarrays, the researchers noticed that the two families “don’t directly regulate each other,” says Blelloch. They are “stabilizing the fates, rather than controlling the switch,” he says.
The future:
The authors “suggest that microRNAs could be used to maintain or induce stemness,” an approach that could be useful in the clinic, wrote F1000 faculty member Martine Roussel in her review. Indeed, Blelloch says he’d like to explore whether this microRNA antagonism is also active in differentiated cells.
F1000 evaluator: W. Hu and J. Coller (Case Western Reserve Univ. Medical Center) • A. Singh and S. Dalton (Univ. of Georgia) • M. Roussel (St. Jude Children’s Research Hospital) •
M. Niessen and C. Niessen (Univ. of Cologne)
Visit the complete F1000 review of this paper.
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