Pluripotent stem cells as a model to study non-coding RNAs function in human neurogenesis

As fine regulators of gene expression, non-coding RNAs, and more particularly micro-RNAs (miRNAs), have emerged as key players in the development of the nervous system. In vivo experiments manipulating miRNAs expression as neurogenesis proceeds are very challenging in the mammalian embryo and totally impossible in the human. Human pluripotent stem cells (hPSCs), from embryonic origin (hESCs) or induced from adult somatic cells (iPSCs), represent an opportunity to study the role of miRNAs in the earliest steps of human neurogenesis in both physiological and pathological contexts. Robust protocols are now available to convert pluripotent stem cells into several sub-types of fully functional neurons, recapitulating key developmental milestones along differentiation. This provides a convenient cellular system for dissecting the role of miRNAs in phenotypic transitions critical to brain development and plasticity that may be impaired in neurological diseases with onset during development. The aim of this review is to illustrate how hPSCs can be used to recapitulate early steps of human neurogenesis and summarize recent reports of their contribution to the study of the role of miRNA in regulating development of the nervous system.