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Chunk #27 — Discussion

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Spontaneous ATM Gene Reversion in A-T iPSC to Produce an Isogenic Cell Line.
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Analysis of TCRβ signatures predicts that several initial “founder” clones of iPSC were present at P4 but that these resolved to a single clone by P20. This was somewhat surprising, as it is often assumed that individually picked colonies of iPSC are derived from a single cell and are therefore clonal. Our results demonstrate that this is not the case. In other studies, we found that multiple founder cells are found in most iPSC colonies using both T cell receptor rearrangement and by mixing source cells of different gender. There was no overt selection for ATM reversion among the multiple founder cell-derived iPSC, although we presume that the gain of ATM function, with its diverse roles regulating cell cycle, DNA repair, and epigenetic mechanisms, may have a selective advantage in the stressful environment of culture.