Role of innate immune signaling in nuclear reprogramming

In 2012 Shinya Yamanaka received the Nobel Prize for his discovery of four transcriptional factors that could induce pluripotency when overexpressed in somatic cells. Recently our lab discovered that innate immune signaling is also critical for this process (Lee et al., Cell 151:547-558, 2012). Specifically, we found that activation of the TLR3-NFκB pathway is required for efficient reprogramming by modulating the expression of epigenetic modifiers to favor an open chromatin configuration. Our unpublished data also suggest that activation of other pattern recognition receptors such as TLR4 or RIG-1 may facilitate reprogramming. Transdifferentiation of one somatic cell to another lineage is another form of nuclear reprogramming. We have shown that transdifferentiation of human fibroblasts to endothelial cells, another form of nuclear reprogramming, also requires innate immune signaling (Sayed et al., Circulation 131:300-309, 2015). Thus innate immune signaling plays a key role in nuclear reprogramming by regulating epigenetic plasticity (Fig. 9.1 ).