Normal (wild type) or microRNA-null (DGCR8 -/-) ESCs with different combinations of individual miRNAs re-introduced and then stained for a marker of pluripotency.
Opposing microRNA families regulate self-renewal in mouse embryonic stem cells
Published 2010 in Nature
Collin Melton, Robert L Judson, Robert Blelloch
Collin Melton performed screens for microRNAs that caused ESCs to differentiate. He found that the miRNA family, Let-7, induced differentiation in ESCs that lacked all endogenous miRNAs, but not in wild type ESCs. His conclusion - there must be an endogenous miRNA family that stabilizes the pluripotency program against Let-7-induced differentiation. He went on to identify this family (the miR-294/302 family), and to identify a network of Let-7-regulated genes, a network of miR-294-regulated genes, and even a set of genes inversely regulated by the two families. We also found that endogenously expressed Let-7 stabilized differentiated cells against re-acquiring the pluripotency program. In short, two conserved miRNA families, each stabilizing the programs of the cell type in which they are normally expressed, and each destabilizing the programs of cell types in which they are normally silenced.