Transcriptomic profiling in human neural progenitor cell-based model of LNSS.

To investigate molecular mechanisms underlying neurodevelopmental defects observed in LNSS, we introduced a KRAS p.G12V-fused destabilizing domain (DD) construct into neuronal progenitor cells (NPCs) derived from H9 human embryonic pluripotent stem cells by lentiviral transduction. In this project, we aimed to profile transcriptional changes in response to TMP-mediated DD-KRAS p.G12V stabilization in cells of two key stages, neural progenitors and differentiating neurons. We also characterized the reversible transcriptional changes after the clearance of DD-KRAS p.G12V in neuronal progenitor and differentiating neurons.