Scientific Publications by FDA Staff

Stem Cells 2018 Oct;36(10):1501-13

High basal levels of gammaH2AX in human induced pluripotent stem cells are linked to replication-associated DNA damage and repair.

Vallabhaneni H, Lynch PJ, Chen G, Park K, Liu Y, Goehe R, Mallon BS, Boehm M, Hursh DA

Human induced pluripotent stem cells (iPSCs) have great potential as source cells for therapeutic uses. However, reports indicate that iPSCs carry genetic abnormalities, which may impede their medical use. Little is known about mechanisms contributing to intrinsic DNA damage in iPSCs that could lead to genomic instability. In this report, we investigated the level of DNA damage in human iPSC lines compared to their founder fibroblast line and derived Mesenchymal Stromal Cell (MSC) lines using ¿H2AX as a marker of DNA damage. We show that human iPSCs have elevated basal levels of ¿H2AX which correlate with markers of DNA replication: EdU and the single-strand binding protein, RPA. ¿H2AX foci in iPSCs also colocalize to BRCA1 and RAD51, proteins in the homologous repair pathway, implying ¿H2AX in iPSCs marks sites of double strand breaks. Our study demonstrates an association between increased basal levels of ¿H2AX and the rapid replication of iPSCs.