Reprogramming Suppresses Premature Senescence Phenotypes of Werner Syndrome Cells and Maintains Chromosomal Stability over Long-Term Culture.

[werner syndrome]

Werner syndrome (WS ) is a premature aging disorder characterized by chromosomal instability and cancer predisposition . Mutations in WRN are responsible for the disease and cause telomere dysfunction , resulting in accelerated aging . Recent studies have revealed that cells from WS patients can be successfully reprogrammed into induced pluripotent stem cells (iPSCs ). In the present study , we describe the effects of long -term culture on WS iPSCs , which acquired and maintained infinite proliferative potential for self-renewal over 2 years . After long -term cultures , WS iPSCs exhibited stable undifferentiated states and differentiation capacity , and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency . WS iPSCs also showed recapitulation of the phenotypes during differentiation . Furthermore , karyotype analysis indicated that WS iPSCs were stable , and half of the descendant clones had chromosomal profiles that were similar to those of parental cells . These unexpected properties might be achieved by induced expression of endogenous telomerase gene during reprogramming , which trigger telomerase reactivation leading to suppression of both replicative senescence and telomere dysfunction in WS cells . These findings demonstrated that reprogramming suppressed premature senescence phenotypes in WS cells and WS iPSCs could lead to chromosomal stability over the long term . WS iPSCs will provide opportunities to identify affected lineages in WS and to develop a new strategy for the treatment of WS .

Diseases
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Diseases presenting "premature upregulation" symptom

werner syndrome

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