Insight into the difficulties of regenerative medicineResearchers discover a major organic mechanism that limits how human cells change their identity Cell can not go back to being Aunts, transformation incomplete.
Cellular Identity Crisis
Cellular reprogramming that is, the conversion of one type of adult cell to another type of adult cell has been championed as a whole new approach to regenerative medicine. But a new study, published today in the Proceedings of the National Academy of Sciences, has found that there’s a major roadblock to making this happen.
Newly reprogrammed cells often relapse and lose their identity over time In the studies, even though researchers were able to quickly convert cells — for example, they could turn skin cells into heart cells in a dish–these newly reprogrammed cells would quickly begin losing their new identity. This incomplete reprogramming makes those cells unsuitable for long-term applications as they still carry much of the genetic set-up associated with an undifferentiated state.
Our understanding of how we might resolve this quandary is founded on the DNA methylation signatures that characterise which cell should be what and do what. From a study conducted by researchers at the Hebrew University and the University of Pennsylvania, it was found that despite large changes in gene expression (which genes are turned ‘on’ or ‘off’), reprogrammed cells remain only partly reprogrammed or keep their original developmental memory authored in DNA methylation patterns.
This suggested to researchers that the normal regulation of gene activity — in this case, by creating open and closed chromatin regions — is a wall preventing the cells from reversing their cellular identity and becoming completely dedicated to their new function. Consequently the reprogrammed cells become trapped in a halfway house between stem cell and functional adult cell.
Untangling the Molecular Hurdles
To do this, the researchers created a new method to examine how DNA methylation is changing when cells are converted in the lab and in animal tissues. They thus reveal the underlying causes that could block reprogramming in order to convert somatic cells en masse.
While many genes change expression, the reprogrammed cells do not totally rewrite their developmental history. We do so in such a way that gives them little space to completely engage with their new role,” said Professor Yosef Buganim of the Hebrew University.
This according to the study may entail that the developmental constraints within DNA regulatory regions do not allow cells to reset these patterns and in doing so partially alter the reprogrammed state. This discovery provides new insights into the molecular hurdles to full de-differentiation of somatic cells.
The researchers, led by Professor Howard Cedar of the Hebrew University Institute for Medical Research-Israel Canada (IMRIC), concluded that these results are a “first step in understanding what underlies stable cell transformation” using this model system, which is important for potential therapeutic use as well. This puts us one step closer to finding a way to bypass these barriers, and that could mean a lot for tissue regeneration and disease modeling.
Conclusion
This study, a breakthrough in cellular reprogramming, provides the first glimpse into what these states mean from a genomic perspective. They also dove deep into the nitty-gritty complications that prevent cells from truly accepting their new selves, which will ultimately benefit researchers hoping to sooth these hurdles. The findings would unlock new paths to achieve efficient and robust cell fate conversions, which in the long run can improve progress in the field of regenerative medicine, tissue engineering and disease modeling.
