In fairy tales, only a magic wand could turn a frog into a prince or a mouse into a horse! But in the real world, turning one living being into another is not so easy. In recent years, scientists have discovered how to do this, using tiny individual living cells: induced pluripotent stem cells. Scientists are able to return adult cells to the embryonic state and then manipulate them to recreate a particular tissue. Today, a new model could eliminate this tedious process, removing the intermediate step and directly programming the cells to become what we want them to become. Magic!?
" Ahe cells in our body always specialize on their own.my ", explained bioinformatics researcher Indika Rajapakse from the University of Michigan. « What we're proposing could be a shortcut to help any cell become a targeted cell type.... »
The roots of this new research framework go back to the discovery of induced pluripotent stem cells and the work of researchers at the Fred Hutchinson Cancer Research Centre in 1989, which led to a method for transforming adult skin cells into muscle cells.
In fact, the team behind this method won the Nobel Prize for discovering how to take an ordinary human skin cell and turn it into a stem cell, a cell similar in type to those in the embryo. With hard work, these cells can grow to become any other type of cell in the body. Over the past decade, this time-consuming transformation technique has led to discoveries about many diseases, from birth defects to cancer.
But what if scientists could take a shortcut and go directly from a skin cell to any other cell?
A new article, published in Proceedings of the National Academy of SciencesThe second technique, which produces induced pluripotent stem cells, outlines one way to do this - and to avoid all the intermediate steps involved in the other technique, which produces induced pluripotent stem cells.
To achieve this feat, scientists exposed cells to a protein called transcription factor (TF), which helps regulate the expression of genes in cells, determine the type of cells they become, as well as cell division, growth and death.
In the 1989 research, the team worked with a TF molecule called MyoD, and the team that discovered the technique to induce pluripotent stem cells did so by manipulating cells with TFs called POU5F1, SOX2, KLF4 and MYC.
Today, Rajapakse and his fellow researchers have taken this research on TFs and combined it with new approaches to DNA and genome structures to develop a mathematical algorithm that they believe successfully predicts the factors known to reprogram cells.
In other words, rather than using one or a few TFs to manipulate cells towards differentiation, their model relies on 3D representations of the genome (called Hi-C data) to map the right timing and sequence of TF injection to produce the specific cell types desired.
" We now have so much data on the activity of RNAs and transcription factors, as well as information on chromosome configuration obtained from high-level data that tells us how often two pieces of chromatin are in close proximity to each other, that we believe we can move from the initial configuration of the cell to the desired configuration. ", explains Mr. Rajapakse.
Such research is particularly exciting because it could not only hypothetically help us produce all kinds of needed tissues, but also help us transform the approach of doctors to diseases such as cancer and genetic disorders by helping them reprogram the very cells that make tissues malignant or dangerous into something benign and safe.
At present, much of the work is theoretical and hasn't been done in a laboratory setting, but Rajapakse and her team are now looking to implement experiments, as well as publish their research, so that other scientists will also be able to use the algorithm - whether to fight cancer, or to push the model into other areas.
" This algorithm provides a blueprint that has important implications for cancer, in that we believe that cancer stem cells can be derived from normal stem cells through similar reprogramming pathways. "says Max Wicha, a stem cell biologist and professor of oncology at the University of Michigan, who co-authored the PNAS article.
" This work also has important implications for regenerative medicine and tissue engineering, as it provides a model for the generation of any type of cells. "he continues. « It also demonstrates the beauty of combining mathematics and biology to unravel the mysteries of nature.. »