Characteristics Of Neural Progenitor Cells Research Articles

Astrocyte-like subpopulation of NG2 glia in the adult mouse cortex exhibits characteristics of neural progenitor cells.

Glial cells expressing neuron-glial antigen 2 (NG2), also known as oligodendrocyte progenitor cells (OPCs), play a critical role in maintaining brain health. However, their ability to differentiate after ischemic injury is poorly understood. The aim of this study was to investigate the properties and functions of NG2 glia in the ischemic brain. Using transgenic mice, we selectively labeled NG2-expressing cells and their progeny in both healthy brain and after focal cerebral ischemia (FCI). Using single-cell RNA sequencing, we classified the labeled glial cells into five distinct subpopulations based on their gene expression patterns. Additionally, we examined the membrane properties of these cells using the patch-clamp technique. Of the identified subpopulations, three were identified as OPCs, whereas the fourth subpopulation had characteristics indicative of cells likely to develop into oligodendrocytes. The fifth subpopulation of NG2 glia showed astrocytic markers and had similarities to neural progenitor cells. Interestingly, this subpopulation was present in both healthy and post-ischemic tissue; however, its gene expression profile changed after ischemia, with increased numbers of genes related to neurogenesis. Immunohistochemical analysis confirmed the temporal expression of neurogenic genes and showed an increased presence of NG2 cells positive for Purkinje cell protein-4 at the periphery of the ischemic lesion 12 days after FCI, as well as NeuN-positive NG2 cells 28 and 60 days after injury. These results suggest the potential development of neuron-like cells arising from NG2 glia in the ischemic tissue. Our study provides insights into the plasticity of NG2 glia and their capacity for neurogenesis after stroke.

Roots of the Malformations of Cortical Development in the Cell Biology of Neural Progenitor Cells.

The cerebral cortex is a structure that underlies various brain functions, including cognition and language. Mammalian cerebral cortex starts developing during the embryonic period with the neural progenitor cells generating neurons. Newborn neurons migrate along progenitors’ radial processes from the site of their origin in the germinal zones to the cortical plate, where they mature and integrate in the forming circuitry. Cell biological features of neural progenitors, such as the location and timing of their mitoses, together with their characteristic morphologies, can directly or indirectly regulate the abundance and the identity of their neuronal progeny. Alterations in the complex and delicate process of cerebral cortex development can lead to malformations of cortical development (MCDs). They include various structural abnormalities that affect the size, thickness and/or folding pattern of the developing cortex. Their clinical manifestations can entail a neurodevelopmental disorder, such as epilepsy, developmental delay, intellectual disability, or autism spectrum disorder. The recent advancements of molecular and neuroimaging techniques, along with the development of appropriate in vitro and in vivo model systems, have enabled the assessment of the genetic and environmental causes of MCDs. Here we broadly review the cell biological characteristics of neural progenitor cells and focus on those features whose perturbations have been linked to MCDs.

Expression of NFIA and NFIB within the murine spinal cord

The Nuclear factor I proteins comprise a family of transcription factors that are expressed in many developing and mature cell populations, including within the central nervous system. Within the embryonic mouse spinal cord, NFIA and NFIB are expressed by neural progenitor cells lining the central canal, where they act to promote astrocytic and oligodendrocytic lineage specification. Cells lining the mature spinal cord central canal retain characteristics of neural progenitor cells, but the expression of NFIA and NFIB within the mature spinal cord at a cell-type-specific level remains undefined. Here, we investigated where these two transcription factors are expressed within the adult mouse spinal cord. We reveal that both factors are expressed in similar cohorts of mature cells, including ependymal cells, interneurons and motor neurons. We also show robust and widespread expression of NFIA and NFIB within nestin-expressing cells following injury to the spinal cord. Collectively, these data provide a basis to further define what functional role(s) NFIA and NFIB play within the adult spinal cord.

In Utero Exposure to Valproic Acid Induces Neocortical Dysgenesis via Dysregulation of Neural Progenitor Cell Proliferation/Differentiation.

This study provides new insight into the mechanisms of how an altered in utero environment, such as drug exposure, affects the generation of neurons prenatally. The antiepileptic drug valproic acid (VPA) is a good target molecule as in utero exposure to VPA has been repeatedly reported to increase the risk of nervous system malformations and to impair higher brain functions in children. We show that VPA decreases the probability of differentiation of the neural progenitor cells (NPCs) in mice, resulting in an abnormally increased number of projection neurons in the superficial layers of the neocortex. Further, we suggest that histone deacetylase inhibition by VPA may be involved in the dysregulation of proliferation/differentiation characteristics of NPCs.

Transplantation of Human Retinal Pigment Epithelium Cells in the Treatment for Parkinson Disease

To assess the clinical effect of transplantation of human retinal pigment epithelial (hRPE) cells into the unilateral postcommissural putamen for treatment for Parkinson disease (PD). Cells from postmortem human eye tissue (10-20weeks of gestation) were cultured in vitro. Cells from -generation passage were implanted in PD postcommissural putamen with stereotactic operation in 12 patients with PD. All patients tolerated surgery well, and no major adverse events occurred. Eleven patients showed improvement in the primary outcome measure at 3months post-treatment, particularly the Unified Parkinson's Disease Rating Scale-M score in the off state. Response reached a peak at 12months and declined during the next 24months. At the 36-month endpoint, there were eight patients who felt better than at baseline. Positron emission tomography (PET) showed a trend with increased dopamine (DA) release during the first 6months. Human retinal pigment epithelial cells have the characteristics of neural progenitor cells and can be induced to differentiate into DA neurons. The results of this clinical trial suggest that the treatment of transplanted hRPE cells could improve symptoms of PD. These cells might serve as a useful source of DA neurons for neural graft in the treatment for PD.

Control of neurogenesis and tyrosine hydroxylase expression in neural progenitor cells through bHLH proteins and Nurr1

The production of dopamine (DA) neurons from neural progenitor cells (NPC) is of particular interest as these neurons degenerate in Parkinson’s disease. Here, we report that the characteristics of NPC from the ventral midbrain (NPC VM) and the striatum (NPC STR) are intrinsically determined. A detailed analysis of the VM during development revealed Ngn2 and Mash1 expression in a DA progenitor domain. Interestingly, over-expression of either Ngn2 or Mash1 induced neurogenesis from expanded NPC VM. Whereas Ngn2 inhibited cell division and the production of neurons even in the presence of mitogens, Mash1 allowed the progenitors to divide while retaining neurogenic potential. However, none of the new neurons derived by over-expressing Ngn2 or Mash1 were positive for DA neuronal markers such as tyrosine hydroxylase. Nurr1 over-expression increased TH levels in a dose-dependant manner within both neurons and glia, suggesting a non-neuronal-specific activation of this enzyme by Nurr1. Double infection with Nurr1 and either Ngn2 or Mash1 resulted in the production of small numbers of TH + neurons, which were larger in size when derived from NPC VM compared to NPC STR. These data provide proof of concept that over-expression of multiple transcription factors can drive the fate of NPC first towards neurons, and then towards the DA phenotype. However, further factors may be required to generate fully functional DA neurons.