Induction of typical and atypical neurogenesis in the adult substantia nigra after mouse embryonic stem cells transplantation. (1st June 2019)

• Record Type: Journal Article
• Authors: Arzate, Dulce María; Guerra-Crespo, Magdalena; Covarrubias, Luis
• Is Part Of: Neuroscience. Volume 408(2019)
• Page Start: 308
• Page End: 326
• Publication Date: 2019-06-01
• Subjects: SN substantia nigra -- EBs embryoid bodies -- EBCs embryoid body cells -- ESCs embryonic stem cells -- MEFs mouse embryonic fibroblasts -- NPCs neural precursor cells -- NSCs neural stem cells -- dpt days post-transplantation -- dpi days post-injection -- SGZ subgranular zone -- SVZ subventricular zone -- Lif leukemia inhibitory factor -- Fgf2 fibroblast growth factor -- Vegf vascular endothelial growth factor -- Egf epidermal growth factor -- Egfp enhanced green fluorescent protein -- CypA cyclosporine A; neurogenesis -- astrocytes -- substantia nigra -- transdifferentiation -- transplantation; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.03.042
• Languages: English
• ISSNs: 0306-4522

Abstract

Abstract: Neurogenesis in the substantia nigra (SN) has been a controversial issue. Here we report that neurogenesis can be induced in the adult rodent SN by transplantation of embryoid body cells (EBCs) derived from mouse embryonic stem cells. The detection of Sox2 + dividing (BrdU + ) putative host neural precursor cells (NPCs) between 1 and 6 days post-transplantation (dpt) supported the neurogenic capacity of the adult SN. In agreement with the awakening of NPCs by EBCs, only host cells from implant-bearing SN were able to generate neurosphere-like aggregates in the presence of Egf and Fgf2. Later, at 15 dpt, a significant number of SN Dcx + neuroblasts were detected. However, a continuous BrdU administration after transplantation showed that only a fraction (about 20–30%) of those host Dcx + progeny derived from dividing cells and few BrdU + cells, some of them NeuN +, survived up to 30 dpt. Unexpectedly, 25–30% of Dcx + or Psa-Ncam + cells at 15 dpt displayed astrocytic markers such as Gfap and S100b. Using a genetic lineage tracing strategy, we demonstrated that a large proportion of host Dcx + and/or Tubb3 + neuroblasts originated from Gfap + cells. Remarkably, new blood vessels formed in association with the neurogenic process that, when precluded, caused a reduction in neuroblast production. Accordingly, two proteins secreted by EBCs, Fgf2 and Vegf, were able to promote the emergence of Dcx + /Psa-Ncam +, Tubb3 + and NeuN + /BrdU + cells in vivo in the absence of EBCs. We propose that the adult SN is a mostly silent neurogenic niche with the ability to generate new neurons by typical and atypical mechanisms. Graphical abstract: Unlabelled Image Highlights: Cells derived from embryonic stem cells stimulate neurogenesis in the substantia nigra (SN) of the adult brain. Astrocytes could transdifferentiate into neurons in the SN. New blood vessels can contribute to activate neurogenesis in the SN.