Minimizing far-extending chromatin perturbation in genome editing preserves stem cell identity - PubMed
6 hours ago
- #chromatin architecture
- #stem cells
- #genome editing
- CRISPR-Cas9 genome editing can cause premature differentiation in neural and embryonic stem cells, even when edits are far from regulatory elements.
- Editing-induced chromatin accessibility changes vary by cell type, with stem cells experiencing extensive perturbations over hundreds of kilobases.
- Local DNA perturbations disrupt CTCF- and condensate-associated chromatin architecture, leading to distal transcriptional changes and loss of stemness.
- Refined gene-editing strategies, including distance-aware sgRNA design and pharmacological approaches, minimize chromatin perturbations and preserve cell identity.
- The study supports safer and broader application of genome-editing technologies by addressing chromatin-related complications.