Telomere dynamics in induced pluripotent stem cells: Potentials for Human disease modeling

Recent advances in reprograming somatic cells from normal and diseased tissues into induced pluripotent stem cells (iPSCs) provide exciting possibilities for generating renewed tissues for disease modeling and therapy. However, questions remain on whether iPSCs still retain certain markers (e.g. aging) of the original somatic cells that could limit their replicative potential and utility. A reliable biological marker for measuring cellular aging is telomere length, which is maintained by a specialized form of cellular polymerase known as telomerase. Telomerase is composed of the cellular reverse transcriptase protein, the integral RNA component, and other cellular proteins (e.g. dyskerin). Mutations in any of these components of telomerase can lead to a severe form of marrow def iciency known as dyskeratosis congenita (DC). This review summarizes recent f indings on the effect of cellular reprograming via iPS of normal or DC patient-derived tissues on telomerase function and consequently on telomere length maintenance. The potentials and challenges of using iPSCs in a clinical setting will also be discussed.