Transcriptional profiling of mouse embryonic stem cells without Huntingtin (Htt). Mus musculus

Mutation in the huntingtin (HTT) gene causes Huntington’s disease. Wild type Htt is essential for development as Htt knockout mice die at day E7.5. Increasing evidence suggests mutant Htt may alter neurogenesis and development of striatal neurons resulting in neuronal loss. Using mouse embryonic stem cells (mESCs), we examined the role of Htt in neural differentiation. We found Htt-null (HN) mESCs inefficient in generating neural stem cells. In contrast differentiation into progenitors of mesoderm and endoderm lineages was not affected. To investigate the basis for the lack of neural differentiation, we carried out gene expression profiling by RNA-seq to examine if genes involved in neural differentiation were dysregulated in HN mESCs. Overall design: Gene expression profiles of R1 wild type and Htt-null (HN) mESCs were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.