The role of HNRNPU and the nuclear matrix in human pluripotent stem cells [ATAC]

During early embryogenesis the fertilized zygote proceeds through an intricate developmental program, accompanyed by DNA and chromatin remodelling. However, the mechanisms governing this reconfiguring are poorly understood. Parts of the embryogenesis developmental program can be captured in vitro in the form of two types of human pluripotent stem cells (hPSC): naïve and primed hPSCs. Naïve hPSCs resemble the inner cell mass of the blastocyst, whilst primed hPSCs resemble the post-implantation embryo. The nucleus is made of DNA wrapped around chromatin, and the nuclear matrix, a proteinaceous gel that provides structure. Here, we show that disruptions in the nuclear matrix caused primed hPSCs to spontaneously convert to the naïve, earlier embryonic state. ATAC-seq was performed on hPSCs (H1 lines) transfected with shRNAs targetting either luciferase (shLUC) as a control, or HNRNPU (shHNRNPU)