The syndrome interferes with “telomerase”, which prevents chromosome from unraveling when cells divide, leading to early aging. In contrast, induced stem cells possess stable telomerase levels and reproduce endlessly as a defining characteristic. So, Agarwal and colleagues attempted to grow, or “reprogram”, induced stem cells from the patient’s skin cells.
“Our results demonstrate that reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting telomerase, and show that strategies to increase (telomerase gene) expression may be therapeutically beneficial,” report the researchers. In theory, a transplant of such induced cells could help treat the syndrome, without the need for immune rejection drugs.
Induced stem cells are grown from skin cells, reprogrammed by infection with four growth-related genes. They resemble embryonic stem cells, which possess the “pluripotent” capability to grow into all types of tissues.
In the Nature study, the team shows that both human induced stem cells and embryonic stem cells increase telomerase with each generation of cells, unlike dyskeratosis congenita cells that die within four generations. During induced cell reprogramming, they found, two of the four new genes appear to overwrite the mutated gene responsible for the syndrome in the new cells. That makes telomerase produced by RNA, the helper molecule for DNA in cells, increase with each generation.
Just such genetic overwriting may help explain why stem cells reproduce endlessly in the lab, suggest the authors. “We have discovered novel mechanisms of regulation of telomerase activity in the pluripotent state, thus illustrating the value of disease-specific (induced) cells,” they conclude.