Figure 5:A working model for Dgcr8 in ESC heterochromatin silencing. Before differentiation, both WT and KO ESCs can maintain proper genome structure with moderate heterochromatin. However, KO ESCs are lacking a large population of small RNAs. Upon differentiation, in WT ESCs the endo-siRNA is blocked while KO cells are defective in this heterochromatin inactivation, which results in accumulation of long dsRNA. Long dsRNAs activate the interferon response via TLR8/9, leading to an arrest in differentiation and apoptosis.