Phenotypic Rescue Of Induced Pluripotent Stem Cells From Dyskeratosis Congenita Patients By Ectopic Expression Of Dkc1 But Not Terc

Telomerase is a ribonucleoprotein that adds telomeric repeats onto the chromosome ends, preventing the replication-dependent loss of telomere repeats and cellular senescence in highly proliferative germ-line cells and in stem cells and cancer cells. Dyskeratosis Congenita (DC) is a rare bone marrow failure syndrome, which affects tissues that need constant renewal by stem cell activity. So far 8 genes have been found whose mutation causes DC and they all encode products that play a role in telomere maintenance. About 35% of DC patients show X-linked-recessive inheritance due to mutations in the DKC1gene encoding dyskerin, a protein important in telomere maintenance and ribosomal RNA biogenesis. Mutant dyskerin can destabilize telomerase RNA leading to rapidly shortening telomeres, accelerated stem cell aging and bone marrow failure. However the precise mechanism by which this occurs is not known and some results suggest dyskerin may play a more direct role in telomerase action. So far studies of the cell biology of DC stem cells have been hampered by their scarcity in patients and their short life span and attempts to create mouse models have suffered from differences in both telomere biology and hematopoiesis between mouse and human.