Mohammadpour H, Brown LK, Hickman D, Briggs LA, Andrews WH, Burke P, Wang T, Foster CA.

Telomerase is a specialized ribonucleoprotein complex, consisting of a telomerase reverse transcriptase protein component (hTERT) and an RNA component (hTR), which adds telomeric TTAGGG repeats at the chromosome tips. Telomerase is expressed in stem cells, germ cells, cancer cells and some rapidly proliferating cells while being undetectable in most somatic cells. The lack of telomerase expression in normal somatic cells leads to cellular aging and senescence due to telomere shortening. It is not understood what causes telomerase to downregulate during human development but de-differentiation of fibroblast into stem cells may provide some insights. Several groups have recently reported that fully differentiated human fibroblasts can be reprogrammed with defined factors (eg. OCT4, SOX2, NANOG, and LIN28) into pluripotent stem cells that express the human telomerase gene (hTERT). At Sierra Sciences, LLC., several Lentiviral constructs, carrying different combinations of the aforementioned genes, were made in order to study the timeline of induction and the minimal number of genes needed to derepress the hTERT gene. This project is considered a first step toward a better understanding of telomerase regulation.