New research at Stowers Institute of Medical Research says that regulatory genes, competing for each other, talk to maintain the balance of cell state. The study was published online on June 5, 2017, in the Proceedings of the National Academy of Sciences. It provides evidence of direct cross-regulatory feedback, or cross-talk, between Nanog and Hox genes.
Nanog regulates cell pluripotency whereas; hox genes control the differentiation of the cell. Pluripotent cells have the capacity of self-renewal. They potentially change into any of a number of cell types. On the other hand, when cells differentiate, they become a more specialized cell type, like heart, brain, or skin cells. In adult organisms, keeping an equilibrium between these two states is very important. This is because it keeps many tissues in a balanced state.
For example, the blood supply has cells that are differentiating, dying, or being repaired. However, a stored/reserved population of “blood-producing adult stem cells” is needed to help replace them. The research team at Stowers suggests that a balance between pluripotency and differentiation pivots in part on regulatory communication that involves inhibition between Nanog and Hox genes. Researchers compare this cross-talk to parents instructing their children.
Just like parents instruct their children for numerous tasks, in the same way, the cross-talk between genes work. It reinforces the importance of instructions and minimizes the negative outcomes. Note that both positive and negative instructions are equally important.
Nanog and Hox genes work as per their distinct jobs. However, by inhibiting each other they work together and direct the proper balance of cellular states. Furthermore, they help the cell to avoid wrong turns and stay on course.
Further analysis of the experimentation
Differentiation and pluripotency are well-studied and popular processes. This study actually links the processes together. And it is pretty surprising because the scientists did not know that these pathways were talking to each other.
The researchers had been studying Hox genes in the early stages of mouse embryonic stem cell differentiation, while they made the discovery. These two respective architect genes control the layout of a developing embryo. In addition, they play a key role in the establishment of the basic body plan and craniofacial development.
The test subject underwent retinoic acid treatment. At two hours and 12 hours of the treatment, the research team found that both Hox and Nanog genes bound to many of the same target sites in the cell. This indicates the regulatory cross-talk between the pluripotency and differentiation pathways. In addition, depending on the context, Hox and Nanog were observed to repress each other. The findings of the study depict the cell states to be more plastic than a fixed program.
“Over the past two decades, biologists have shown that cells are actively assessing their environment. They have numerous fates to choose from. The regulatory loops exposed by the study enumerate how the dynamic nature of cells is being maintained.
This remarkable work, by the Stowers team, provides important insight into the basic processes of tissue formation. Moreover, it holds relevance for the field of regenerative medicine and the development of therapeutic approaches for certain cancers.