Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex

• DOI: 10.1016/j.stem.2016.10.020
• Publication Date: 2016-11-23T21:17:36Z
• Authors: Francesco Bifari; Ilaria Decimo; Annachiara Pino; Enric Llorens-Bob...; Sheng Zhao; Christian Lange; Gabriella Panuccio; Bram Boeckx; Bernard Thienpont; Stefan Vinckier; Sabine Wyns; Ann Bouché; Diether Lambrechts; Michele Giugliano; Mieke Dewerchin; Ana Martin-Villalba; Peter Carmeliet
• Keywords: Cerebral Cortex; Neurons; Gene Expression Profiling; Neurogenesis; Reproducibility of Results; Cell Differentiation; Embryo, Mammalian; PDGFRβ; electrophysiology; lineage tracing; meninges; neonatal cerebral cortex; neural progenitors; neurogenesis; radial glia cells; single-cell RNA sequencing; Excitatory Amino Acid Transporter 1; Mice, Inbred C57BL; Nestin; Receptor, Platelet-Derived Growth Factor beta; HEK293 Cells; Meninges; Animals, Newborn; Cell Movement; Animals; Humans; Cell Lineage; electrophysiology; lineage tracing; meninges; neonatal cerebral cortex; neural progenitors; neurogenesis; PDGFR; radial glia cells; single-cell RNA sequencing; Single-Cell Analysis; Neuroglia

Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2+ neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex.