Nijmegen Breakage Syndrome fibroblasts and iPSCs: cellular models for uncovering disease-associated signaling pathways and establishing a screening platform for anti-oxidants.

ABSTRACT: Nijmegen Breakage Syndrome (NBS) is associated with cancer predisposition, premature aging, immune deficiency, microcephaly and is caused by mutations in the gene coding for NIBRIN (NBN) which is involved in DNA damage repair. Dermal-derived fibroblasts from NBS patients were reprogrammed into induced pluripotent stem cells (iPSCs) in order to bypass premature senescence. The influence of antioxidants on intracellular levels of ROS and DNA damage were screened and it was found that EDHB-an activator of the hypoxia pathway, decreased DNA damage in the presence of high oxidative stress. Furthermore, NBS fibroblasts but not NBS-iPSCs were found to be more susceptible to the induction of DNA damage than their healthy counterparts. Global transcriptome analysis comparing NBS to healthy fibrobla

SUBMITTER: Mlody B 

PROVIDER: S-EPMC5548734 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature