Figure 7.

Simplified Molecular Mechanisms Underlying Fibroblast-to-Neuron Reprogramming

NEUROG2, a pioneer transcription factor, targets thousands of pro-neural genetic elements. Small molecules simultaneously activate signaling cascades that promote NEUROG2 and CREB1 co-transcription, induce SOX4 expression, enhance H3K27 acetylation, and promote SOX4-dependent chromatin remodeling. NEUROG2 and SOX4 synergize to enhance the expression of diverse pro-neural transcription factors and drive neuron identity in diverse fibroblast and glioblastoma cell types.