NEUROD1 (ND1)-induced astrocyte-to-neuron (AtN) conversion shows promise for treating neurological disorders. Researchers established an in vitro reprogramming system for rat cortical astrocytes. The dynamic trajectory and molecular mechanism of the transcription factor NEUROD1(ND1) driving the transdifferentiation of astrocytes (Ast) into neurons (Neu) were systematically analyzed through single-cell and multi-omics sequencing techniques (scRNA-seq, ATAC-seq, Cut&Tag and bulk RNA-seq).
The research found that ND1, as a pioneer factor, reshaps chromatin openness by inducing histone modification of H3K27ac and activates 25 key regulatory targets including Hes6. Its reprogramming process highly simulates cortical neurogenesis in vivo. This research not only clarifies the unique intermediate state cells and core regulatory network during the transdifferentiation of astrocytes into neurons, but also provides a revolutionary strategy for the repair of nerve damage and the treatment of degenerative diseases. In this study, high-quality transcriptome sequencing analysis was completed by using the SURFSeq 5000 platform of GeneMind Bioscience Company Ltd.,
