Transcriptomic profiling in human neural progenitor cell-based model of DNM1L-associated encephalopathy.

To profile the impact of DNM1L dysfunction at the molecular level during the differentiation of neural progenitor cells (NPCs) into neurons, we introduced wild-type DNM1L using a Tet-off system followed by targeted KO of endogenous DNM1L allele by CRISPR-Cas9 prior to NPC differentiation in human embryonic stem cells. In this project, we aimed to profile the transcriptional alterations associated with DNM1L dysfunction by treating with doxycycline across two key stages: neural progenitors and differentiated neurons.To test transcriptomic reversibility during the key stages of human neuronal development, we chemogenetically restored the DNM1L expression by DOX withdrawal during or after early neuronal differentiation (NPC-Rescue or NEU-Rescue, respectively).