Fetal signatures in the 3D genome of iPSC-derived neurons and their implications for disease modeling.

iPSC-derived neurons predominantly retain fetal-like chromatin architecture, showing stronger compartmentalization and developmental gene enrichment at TAD borders compared to mature neurons.

• Why it matters: Understanding how well iPSC-derived neurons mimic authentic brain neurons is crucial for accurate disease modeling, especially for neurodevelopmental disorders, but their chromatin similarities remain unclear.
• What they did: The study processed 96 high-coverage Hi-C contact maps from iPSC-derived and postmortem neurons, analyzing features like compartments, TADs, loops, Polycomb contacts, and FIREs, and compared these across human and mouse samples.
• The result: Findings reveal that iPSC-derived neurons resemble fetal neurons more than mature ones, with implications for their use in modeling neurodevelopmental disease interactions, and provide a valuable resource for future chromatin studies.