Fig. 3: Reactivated embryonic programs in adult diseases: similar yet distinct.

a, Similar but not identical signals, such as growth factors and microenvironmental components, can induce embryonic TFs. b, Due to the differences between embryonic signals and those activated in adult disease, the network of activated TFs, although including many of the same factors, can be substantially distinct. These differences can include the abundance of a TF and ectopic interactions with other factors that are not present in the embryo. Importantly, the dynamic regulation that exists in the embryo can be lost in the reactivated adult context. c, In many cases, embryonic TFs can induce similar downstream genes in the adult (for example, no. 3). However, variabilities can also occur, for instance, if these factors may differentially induce some genes due to alterations in chromatin accessibility (for example, nos. 4 and 6). In addition, varied levels of TFs can induce excess gene expression (for example, no. 2). Altered levels of post-translational modification can also occur in reactivated factors (for example, no. 5). Mutations in the disease can also lead to production of a mutated product (missense, for example, no. 1) or even absence of gene expression (for example, if deleted like in no. 7). d, Similarities and differences between original embryonic genetic programs and those reactivated in the adult can induce similar functional outcomes such as cell proliferation and cell movement, while the differences can make these outcomes uncontrolled and deleterious, for example, during tumor growth and invasion.