An emerging issue in the stem cell field is somatic mosaicism, the presence of DNA structural and/or sequence variation from cell to cell in a given individual. This raises interesting questions about not only the role of this form of cellular heterogeneity in health and disease but also the utility of any single patient-derived iPSC line in accurately representing that patient’s disease state. Alysson Muotri, from University of California, San Diego, presented data on iPSC-derived neurons from patients with Aicardi-Goutieres syndrome (AGS), a neurodevelopmental disease characterized by intellectual and physical problems with neuroinflammation. Muotri made iPSCs from AGS patients with mutations on TREX1 gene related to clearance of L1 mobile elements from the cytosol and compared them with isogenic controls. TREX1-mutant cells have high levels of single-stranded DNA (ssDNA) derived from mobile retroelements (Alus and L1s) in the cytoplasm and decreased expression of neuronal markers TLG4, MAP2, TUJ1, and SYN. These features were partially rescued by treatment with reverse transcriptase inhibitors (such as anti-HIV drugs), indicating clinical relevance on this extreme neurological condition. Additionally, TREX1-deficient astrocytes also increased ssDNA and
