Researchers from the Salk Institute in California, USA, have successfully transformed skin cells into brain cells. The scientists used direct and indirect methods of creating neurons from human skin cells and report that the direct conversion retains the age of the original (skin) cells, offering insight into the aging process in the brain.
The finding that human stem cells could be obtained from non-embryonic sources and induced to become “pluripotent,” and then reprogrammed to yield desired cell types, opened many avenues for future research, apart from winning Dr. Yamanaka a Nobel Prize. These cells, known as induced pluripotent stem cells or iPSCs, lose characteristic age-related cellular signatures (epigenetic signatures-which direct gene expression) when reprogrammed, and revert to their younger selves when transformed. As a result, the study of age-related changes in cell populations arising from iPSCs was a challenge. Research has shown that the readjustment of epigenetic signals could be overcome by bypassing the stem cell stage.
In the current study, skin cells taken from 19 individuals, their ages ranging from newborn to 89 years, were prompted to turn into neurons, via the stem cell step as well as by bypassing the step completely. The results showed that:
- When neurons were derived via the iPSC step, those from young people’s skin cells were comparable to the ones from older subjects.
- However, direct conversion of the skin cells to neurons (termed induced neurons or iNs) retained the age-dependent epigenetic signatures, corresponding to the age of the donor of skin cells.
- A nuclear pore protein molecule known as RanBP17 decreases with age.
- Reduced RanBP17 leads to increased nuclear/cytoplasmic compartmentalization defects, also seen in aging cells.
- Gene expression patterns of iNs derived from older skin cell donors and those from neurons from autopsied brains were comparable.
Discussing the findings, the lead author says in the Salk Institute News, “This lets us keep age-related signatures in the cells so that we can more easily study the effects of aging on the brain.”
One of the co-authors, Dr. Martin Hetzer, adds, “By using this powerful approach, we can begin to answer many questions about the physiology and molecular machinery of human nerve cells–not just around healthy aging but pathological aging as well.”
Whereas taking a sample and analyzing it is doable for other body parts, the brain poses a unique problem. This study solves that problem by devising a method for turning human skin cells to age-matched brain cells. The method offers tremendous possibilities for understanding diseases, such as Parkinson’s disease and Alzheimer’s disease. By converting the patients’ own skin cells to neurons, scientists could elucidate the details of disease development and design/test drugs to combat the same.
Written by Mangala Sarkar, Ph.D.
Mertens, J., Paquola, A., Ku, M., Hatch, E., Bohnke, L., Ladjevardi, S., . . . Gage, F. (2015). Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects. Cell Stem Cell. http://dx.doi.org/10.1016/j.stem.2015.09.001
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