Evidence for premature aging due to oxidative stress in iPSCs from Cockayne syndrome

Cockayne syndrome (CS) is a human premature aging disorder associated with neurological and developmental abnormalities, caused by mutations mainly in the CS group B gene (ERCC6). At the molecular level, CS is characterized by a deficiency in the transcription-couple DNA repair pathway. To understand the role of this molecular pathway in a pluripotent cell and the impact of CSB mutation during human cellular development, we generated induced pluripotent stem cells (iPSCs) from CSB skin fibroblasts (CSB-iPSC). Here, we showed that the lack of functional CSB does not represent a barrier to genetic reprogramming. However, iPSCs derived from CSB patients fibroblasts exhibited elevated cell death rate and higher reactive oxygen species (ROS) production. Moreover, these cellular phenotypes were accompanied by an up-regulation of TXNIP and TP53 transcriptional expression. Our findings suggest that CSB modulates cell viability in pluripotent stem cells, regulating the expression of TP53 and TXNIP and ROS production.

UCSD

UCSD

Emerald Foundation

Emerald Foundation

National Institutes of Health [1-DP2-OD006495-01]

National Institutes of Health

California Institute for Regenerative Medicine (CIRM)

California Institute for Regenerative Medicine (CIRM) [TR2-01814]

CAPES (Coordenacao de Aperfeicoamento de Nivel Superior)

CAPES (Coordenacao de Aperfeicoamento de Nivel Superior) [BEX 4428/08-0]

FAPESP-CEPID (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)

FAPESPCEPID (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)

CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)