Transient matrix remodeling during direct cell-fate reprogramming enables self-assembly of dense neuronal niches

Direct fibroblast-to-neuron reprogramming in collagen microgels compacts the ECM and yields densely packed induced neuron microcultures within the remodeled matrix.

• Why it matters: Native tissues combine high cell density with continuous cell–ECM interactions, but most 3D cultures recreate either dense cell-cell contacts or a defined ECM, not both.
• What they did: Human dermal fibroblasts were embedded in collagen microgels, where intrinsic matrix remodeling drove rapid ECM compaction while contractile fibroblasts were converted into induced neurons (iN).
• The result: The iN microgels combine high cell density, defined ECM composition, and tunable biophysical properties in a scalable microscale format, enabling tissue-like microenvironment engineering during direct reprogramming.