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 from a second family called embryonic stem cell cycle (ESCC) microRNAs into the let-7 ...