Researchers uncover the challenges of converting one type of specialized cell into another, a critical process for advancing regenerative medicine. The study reveals that the developmental constraints embedded in the regulatory regions of DNA prevent cells from fully resetting their original identity, limiting their potential for therapeutic applications.
The Cellular Identity Crisis
Cellular reprogramming, also called trans-differentiation enables scientists converting cells from one type to another example tranforming fibroblasts in the skinn into heart muscle cells but generally this process works extremely inefficiently. The newly reprogrammed cells often abandon their acquired identity with time, but not soon after they are first created.
This question has vexed researchers, because although reprogrammed cells might initially appear to resemble one another (i.e., look and act the same) they cannot become perfect replicas of that cell type. Published in the Proceedings of the National Academy of Sciences, this study aimed to find out what is going wrong here at a molecular level; it reveals that reprogrammed cells have a hard time keeping their new identity as planned.
The Molecular Block to Full Transformation
Research led by Professors Yosef Buganim and Howard Cedar of the Alexander Silberman Institute of Life Sciences at the Hebrew University of Jerusalem, together with Professor Ben Stanger of the Perelman School of Medicine (University of Pennsylvania) developed a new method to study this process. DNA methylation is a chemical process that controls whether genes are on or off, akin to a master control switch for gene expression that locks cells in a particular state.
Thus, by analyzing a suite of lab-grown and animal tissues subjected to different models of direct cell conversion, we surprisingly found that the reprogrammed cells display genome-wide alterations in gene expression yet fail to reset their original developmental blueprint transcribed by DNA methylation. These limitations impair their potential to fully embrace this new role, while the developmental restrictions inscribed in DNA regulatory regions prevent cells from resetting these patterns.
Conclusion
This study constitutes a milestone, as it provides deep knowledge regarding the recurrent bottlenecks in terms of stable and functional cell transformations, which is indispensable for efficient cell-based therapies. These researchers believe that uncovering the molecular barrier that stops reprogrammed cells reversing all the way back to their original identity opens new ways of developing treatments which can battle against such a roadblock. Breakthroughs resulting from this study may soon impact the preparation of far more powerful and quality-assured cell-based therapies as the field of regenerative medicine rapidly advances, opening up an era of personalized medicine.
