Retrotransposons are interspersed repeating sequences that make up over 40% of the human genome. Proper tissue regeneration requires they be tightly regulated, but little is known about how this process is coordinated. To provide insights, researchers led by Yejing Ge, Ph.D., studied laboratory models of hair follicle stem cells in the skin. When injured, these stem cells change to help restore the skin barrier but eventually become exhausted.
The researchers found an epigenetic regulator, SETDB1, driving retrotransposon suppression to protect regeneration. Removing SETDB1 led to the induction of a viral type of retrotransposon along with viral-like particles, resulting in hair loss and stem cell exhaustion. Antiviral drugs reversed this condition and led to hair cell regeneration. The researchers identified at least two involved pathways – antiviral-dependent and independent host responses toward reactivated retrotransposons – which potentially can be leveraged to deter tumor development and innovate cancer treatments.