Total RNA sequencing in neuroprogenitors after SMG6 deletion

Identification of transcriptome changes in neuroprogenitor cells deficient for SMG6 mediated nonsence mediated mRNA decay with the aim to identify specific pathways or single genes causing the observed phenotype. Nestin-cre mediated Smg6 inactivation caused perinatal lethality and defective late cortical neurogenesis due to reduced renewal and survival of the cortical neuroprogenitor cells. However the Emx1-cre mediated deletion only in cortical and hippocampal progenitors did not cause comparable phenotypes. RNAseq identified mainly cell cycle and DNA damage response pathways modulating the transcriptome. FOXM1 was identified as possible upstream regulator of interneuron progenitor fate. Transcriptome comparison of neural stem cells isolated from E13.5 embryo brains. The analysis of in vitro cultures was performed 6 days after the start of 4-OHT treatment (Smg6-iKO). 3 sample groups were evaluated, 1 mutant ("Smg6-iKO") and 2 control groups while the latter two were used to evaluate the effect of 4-OHT: In the mutant Smg6-iKO cells, Smg6 was deleted after 4-OHT treatment (i.e., induced knock-out). The first control group ("control") contains the same cells as in Smg6-iKO but was not treated with 4-OHT. The second group ("control with 4-OHT") contains cells that were treated with 4-OHT but cannot induce Smg6 deletion due to the genotype of the cells.