Impact of c-JUN deficiency on thalamus  development in mice and human neural  models [ATACseq, RNAseq, CUT&Tag]
c-Jun is a gene expression regulator. By forming homo- or heterodimer, c-Jun binds to DNA and regulates gene transcription. c-Jun is deeply involved in embryonic development but its effect on nervous system development especially in higher mammal is unclear. In this study, we combined H1ESC derived neural progenitor cells (NPCs), cerebral organoids (COs),Thalamus Organoids(ThOs) and mouse model to study the role of c-Jun in early nervous system development. c-Jun KO promoted NPCs induction and differentiation while weakened NPCs' adhesion ability. c-Jun KO COs got more robust neural ectoderm and expanded Pax6+/Nestin+ cortex-like layer while less tight junctional core. c-Jun KO mouse embryos on E14.5 showed malformation of thalamus in diencephalon with tight junction loose and cell lose. Taken together, the consistent trend in three models implied that c-Jun deletion promoted neural differentiation while weakened the tight junctions. The thalamus/diencephalon was vulnerable to dysplasia when lose c-Jun in early mouse embryonic development. Overall design: To investigate the function of c-Jun, we established 2 H1ESCs cell lines which the target gene (c-Jun) has been knocked  out by CRISPR/Cas9. H1 ESC cell line used as wild type control. We then induced the 3 cell lines into cerebral organoids, thalamus organoids and performed gene expression profiling anlysis using data obtained from RNA-seq, ATAC-seq. At last, we performed Differential Expression Gene Analysis and Gene Expression Heat Map online using the seq data and did comparation between the wild type and knockout cell lines.