An epigenetic barrier sets the timing of human neuronal maturation

Abstract The pace of human brain development is highly protracted compared with most other species 1–7 . The maturation of cortical neurons is particularly slow, taking months to years to develop adult functions 3–5 . Remarkably, such protracted timing is retained in cortical neurons derived from human pluripotent stem cells (hPSCs) during in vitro differentiation or upon transplantation into the mouse brain 4,8,9 . Those findings suggest the presence of a cell-intrinsic clock setting the pace of neuronal maturation, although the molecular nature of this clock remains unknown. Here we identify an epigenetic developmental programme that sets the timing of human neuronal maturation. First, we developed a…