Now a new model could do away with this time-consuming process, taking out the middle step and directly programming cells to become whatever we want them to be. “What we propose could provide a shortcut to doing the same, to help any cell become a targeted cell type.”
The roots of the new framework go back further than the discovery of induced pluripotent stem cells in 20066, to when researchers at the Fred Hutchinson Cancer Research Centre in 1989 figured out how to turn adult skin cells into muscle cells.
In the 1989 research, the team worked with a TF molecule called MyoD, and the team who discovered the technique to induce pluripotent stem cells did so by manipulating cells with TFs called POU5F1, SOX2, KLF4, and MYC. Now, Rajapakse and fellow researchers have taken that research on TFs and combined it with newer insights into DNA and genome structures, to develop a mathematical algorithm that they say successfully predicts the factors known to reprogram cells.
“We have so much data now from RNA and transcription factor activity, and from Hi-C data of chromosome configuration that tells us how often two pieces of chromatin are near one another, that we believe we can go from the cell’s initial configuration to the desired configuration,” says Rajapakse.
It’s an incredibly exciting framework that could not only hypothetically help us produce all kinds of needed tissues – but it might also help us turn the tables on diseases like cancer and genetic disorders by helping us to reprogram the very cells that make tissue malignant or dangerous into something benign and safe.
“This work also has important implications for regenerative medicine and tissue engineering, since it provides a blueprint for generating any desired cell type,” explains one of the team, stem cell biologist Max Wicha.