| Autor: |
Vallabhaneni, Haritha, Lynch, Patrick J., Chen, Guibin, Park, Kyeyoon, Liu, Yangtengyu, Goehe, Rachel, Mallon, Barbara S., Boehm, Manfred, Hursh, Deborah A. |
| Zdroj: |
Stem Cells; October 2018, Vol. 36 Issue: 10 p1501-1513, 13p |
| Abstrakt: |
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 with their founder fibroblast line and derived mesenchymal stromal cell (MSC) lines using the phosphorylated histone variant, γH2AX, as a marker of DNA damage. We show that human iPSCs have elevated basal levels of γH2AX, which correlate with markers of DNA replication: 5‐ethynyl‐2′‐deoxyuridine and the single‐stranded binding protein, replication protein A. γH2AX foci in iPSCs also colocalize to BRCA1 and RAD51, proteins in the homologous repair pathway, implying γH2AX in iPSCs marks sites of double strand breaks. Our study demonstrates an association between increased basal levels of γH2AX and the rapid replication of iPSCs. Stem Cells2018;36:1501–1513 Increased basal levels of γH2AX, the phosphorylated form of the variant histone, γH2AX, associate with replication in human iPSCS. iPSCs replicate more rapidly than their founding fibroblasts or derived MSCs. The number of replicating cells is low in fibroblasts, but when reprogrammed to iPSCs, the number of cells in S phase increases with a corresponding increase in γH2AX expression. γH2AX expression decreases as the iPSCs are differentiated into slowly dividing MSCs. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Plný text