Transcription profiling of Smarce1- MD (R42A) and Smarce1- MD mESCs, and their derived cell cultures at day 06 after neural induction.

To evaluate the effects of mitotic degradation of SMARCE1 upon gene expression, we performed RNA-sequencing (RNA-seq) of cultures of four independent subclones each of Smarce1-MD and control Smarce1-MD (R42A) mESCs. We found that transcription of the core pluripotency regulatory network was not disrupted. In contrast, GO analysis showed that neural differentiation-associated terms were enriched among genes upregulated in Smarce1-MD mESCs. To better understand the difference in neural fates in the neural induction experiments, we performed differential gene expression analysis and gene set enrichment analysis (GSEA) studies. Mitotic degradation of SMARCE1 resulted in higher expression of GABA receptors and hyper-activation of synaptic signaling on neural induction, indicating the aberrant neural cell fate commitment compared to SMARCE1-MD (R42A) cultures. We performed RNA-seq in Smarce1- MD (R42A) and Smarce1- MD mESCs. We also performed RNA-seq in Smarce1- MD (R42A) and Smarce1- MD derived cultured upon direct neural induction.