The study investigates the role of Dicer, an enzyme that processes double-stranded RNA into small interfering RNAs (siRNAs) and microRNAs (miRNAs), in mouse embryonic stem (ES) cells. By generating Dicer-deficient ES cells through conditional gene targeting, the researchers found that these cells were viable but exhibited severe defects in differentiation both in vitro and in vivo. The Dicer-deficient cells showed reduced silencing of centromeric repeat sequences and homologous small dsRNAs, leading to increased expression of these sequences. Re-expression of Dicer in the knockout cells rescued these phenotypes, suggesting that Dicer is essential for maintaining centromeric heterochromatin structure and silencing. The findings indicate that Dicer plays a crucial role in multiple biological processes, including stem cell differentiation and epigenetic regulation.The study investigates the role of Dicer, an enzyme that processes double-stranded RNA into small interfering RNAs (siRNAs) and microRNAs (miRNAs), in mouse embryonic stem (ES) cells. By generating Dicer-deficient ES cells through conditional gene targeting, the researchers found that these cells were viable but exhibited severe defects in differentiation both in vitro and in vivo. The Dicer-deficient cells showed reduced silencing of centromeric repeat sequences and homologous small dsRNAs, leading to increased expression of these sequences. Re-expression of Dicer in the knockout cells rescued these phenotypes, suggesting that Dicer is essential for maintaining centromeric heterochromatin structure and silencing. The findings indicate that Dicer plays a crucial role in multiple biological processes, including stem cell differentiation and epigenetic regulation.