Multi-omic profiling of 85 iPSC lines from familial dementia reveals cellular diversity and regulators of organoid development.

Whole-genome and transcriptomic profiling of 85 MAPT-mutant iPSC lines reveal unintended editing events and cellular states linked to organoid development.

• Why it matters: Understanding the molecular variability in iPSC lines is crucial for distinguishing disease-related biology from technical and biological variation, especially in modeling neurodegenerative diseases like dementia.
• What they did: The study used whole-genome sequencing, long-read sequencing, bulk and single-cell RNA sequencing, and DNA methylation arrays to analyze 85 iPSC lines, identifying four reproducible cell states and candidate surface markers.
• The result: Unintended editing events and recurrent duplications were linked to altered gene expression and impaired cortical organoid patterning, highlighting the importance of using unconverted lines as controls to improve iPSC-based research.