NG2 cells generate both oligodendrocytes and gray matter astrocytes (original) (raw)
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Glia, 2014
NG2 (nerve/glia antigen-2) is a type I transmembrane glycoprotein and also known as chondroitin sulfate proteoglycan 4. In the parenchyma of the central nervous system, NG2-expressing (NG2 1 ) cells have been identified as a novel type of glia with a strong potential to generate oligodendrocytes (OLs) in the developing white matter. However, the differentiation potential of NG2 glia remained controversial, largely attributable to shortcomings of transgenic mouse models used for fate mapping. To minimize these restrictions and to more faithfully mimic the endogenous NG2 expression in vivo, we generated a mouse line in which the open reading frame of the tamoxifen-inducible form of the Cre DNA recombinase (CreERT2) was inserted into the NG2 locus by homologous recombination. Results from this novel mouse line demonstrate that at different developmental stages of the brain, NG2 1 cells either stayed as NG2 glia or differentiated into OLs during the whole life span. Interestingly, when Cre activity was induced at embryonic stages, a significant number of reporter 1 astrocytes could be detected in the gray matter after birth. However, in other brain regions, such as olfactory bulb, brain stem, and cerebellum, all of the NG2 glia was restricted to the OL lineage. In addition, tamoxifen-sensitive and NG2 gene locus-dependent gene recombination could be detected in a small, but persistent population of cortical NeuN 1 neurons starting from the second postnatal week.
Cytology and lineage of NG2-positive glia
2002
We present evidence that NG2+ glia are an integral part of an oligodendrocyte/synantocyte (OS) lineage stream the progenitors of which begin to produce both glial phenotypes at about birth. The NG2 CSPG is differentially distributed within the OS lineage, being expressed in progenitors and synantocytes but not in oligodendrocytes. All cells in the OS lineage, except the primordial stem cells, express O4. The oligodendrocyte line reacts with CD9, but synantocytes are CD9−. Nonetheless, synantocytes are morphologically complex and specialised glia which contact axolemma in myelinated fibres at nodes of Ranvier and synaptic terminals, and form >99% of all NG2+ glia in the adult CNS. Thus, the other NG2+ phenotype, the adult oligodendrocyte progenitor cell (AOPC), constitutes a small population of <1% of all NG2+ glia in the mature CNS. AOPC are a heterogeneous set of cells probably originating from multiple sources which, by definition, produce oligodendrocytes in the adult to replace loss after trauma, demyelination and normal 'wear and tear'. The definitive functions of synantocytes remain undefined.
Neuron, 2010
The mammalian CNS contains a ubiquitous population of glial progenitors known as NG2 + cells that have the ability to develop into oligodendrocytes and undergo dramatic changes in response to injury and demyelination. Although it has been reported that NG2 + cells are multipotent, their fate in health and disease remains controversial. Here, we generated PDGFαR-CreER transgenic mice and followed their fate in vivo in the developing and adult CNS. These studies revealed that NG2 + cells in the postnatal CNS generate myelinating oligodendrocytes, but not astrocytes or neurons. In regions of neurodegeneration in the spinal cord of ALS mice, NG2 + cells exhibited enhanced proliferation and accelerated differentiation into oligodendrocytes, but remained committed to the oligodendrocyte lineage. These results indicate that NG2 + cells in the normal CNS are oligodendrocyte precursors with restricted lineage potential, and that cell loss and gliosis are not sufficient to alter the lineage potential of these progenitors in ALS mice.
Neuroscience, 2018
NG2 glia are self-renewal cells widely populating the entire central nervous system (CNS). The differentiation potential of NG2 glia in the brain has been systematically studied. However, the fate of NG2 glia in the spinal cord during development and after injury is still unclear. Here, we took advantage of faithful expression of Cre in NG2-CreERT2 knock-in mice to demonstrate that spinal NG2 glia remain committed to the oligodendrocyte (OL) lineage and generate OLs, but not astrocytes or neurons, during development. However, we found significant age- and region dependent differences in differentiation into OLs. Embryonic or neonatal NG2 glia generated more than 90% of the white matter OLs, but only 50% (embryonic) or 75% (neonatal) of gray matter OLs. Such differences disappeared after myelin completion coinciding with a decrease in the differentiation rate. While we never detected the generation of astrocytes from NG2 glia during spinal cord development, we found a small portion o...
Morphological and physiological interactions of NG2-glia with astrocytes and neurons
Journal of Anatomy, 2007
Models of central nervous system (CNS) function have historically been based on neurons and their synaptic contacts – the neuronal doctrine. This doctrine envisages glia as passive supportive cells. However, electrophysiological and imaging studies in brain slices show us that astrocytes, the most numerous cells in the brain, express a wide range of neurotransmitter receptors that are activated in response to synaptic activity. Furthermore, astrocytes communicate via calcium signals that are propagated over long distances by the release of ‘gliotransmitters’, the most abundant being adenosine triphosphate (ATP). This has led to the concept of the neuron–astroglial functional unit as the substrate of integration in the CNS. Recently, a novel glial cell type has been characterized by expression of the proteoglycan NG2. These NG2-glia receive presynaptic input from neurons and responds to neurotransmitters released at synapses. Now, studies on transgenic mice in which fluorescent proteins are specifically expressed by subclasses of glia are helping to address the question of where NG2-glia fit in the neuron–astroglial model of integrated brain function. NG2-glia, as well as astrocytes, have been shown to respond to neuronal and astroglial signals by raised intracellular calcium, which is a potential communications mechanism by which NG2-glia may be active partners in neuron–glial circuits. Moreover, a current concept of NG2-glia considers them to be ‘neural stem cells’ and an exciting prospect is that neuron–glial signalling may regulate the differentiation capacity of NG2-glia and their response to injury.
NG2 cells differentiate into astrocytes in cerebellar slices
Molecular and Cellular Neuroscience, 2009
Glia NG2 Astrocyte OPC Synantocyte Cerebellum NG2-glia are an abundant population of glial cells that have been considered by many to be oligodendrocyte progenitor cells (OPCs). However, growing evidence suggests that NG2-glia may also be capable of differentiating into astrocytes and neurons under certain conditions. Here, we have examined NG2-glia in cerebellar slices, using transgenic mice in which the astroglial marker glial specific protein (GFAP) drives expression of the reporter gene enhanced green fluorescent protein (EGFP). Immunolabelling for NG2 shows that NG2-glia and GFAP-EGFP astroglia are separate populations in most areas of the brain, although a substantial population of NG2-glia in the pons also express the GFAP-EGFP reporter. In the cerebellum, NG2glia did not express EGFP, either at postnatal day (P)12 or P29-30. We developed an organotypic culture of P12 cerebellar slices that maintain cytoarchitectural integrity of Purkinje neurons and Bergmann glia. In these cultures, BrdU labelling indicates that the majority of NG2-glia enter the cell cycle within 2 days in vitro (DIV), suggesting that NG2-glia undergo a 'reactive' response in cerebellar cultures. After 2 DIV NG2-glia began to express the astroglial reporter EGFP and in some cases the respective GFAP protein. However, NG2glia did not acquire phenotypic markers of neural stem cells or neurons. The results suggest that NG2-glia are not lineage restricted OPCs and are a potential source of astrocytes in the cerebellum.
NG2 Glia: Novel Roles beyond Re-/Myelination
Neuroglia, 2018
Neuron-glia antigen 2-expressing glial cells (NG2 glia) serve as oligodendrocyte progenitors during development and adulthood. However, recent studies have shown that these cells represent not only a transitional stage along the oligodendroglial lineage, but also constitute a specific cell type endowed with typical properties and functions. Namely, NG2 glia (or subsets of NG2 glia) establish physical and functional interactions with neurons and other central nervous system (CNS) cell types, that allow them to constantly monitor the surrounding neuropil. In addition to operating as sensors, NG2 glia have features that are expected for active modulators of neuronal activity, including the expression and release of a battery of neuromodulatory and neuroprotective factors. Consistently, cell ablation strategies targeting NG2 glia demonstrate that, beyond their role in myelination, these cells contribute to CNS homeostasis and development. In this review, we summarize and discuss the adv...
Glia, 2001
During early neural development, the lineage specification of initially pluripotent progenitor cells is associated with proliferation, differentiation, and migration. Oligodendroglial progenitor cells migrate from their sites of origin to reach the axons that they will myelinate. We have described a cell-surface protein, AN2, expressed by oligodendroglial progenitor cells in vitro and showed that antibodies against AN2 inhibited the migration of cultured primary oligodendroglial progenitor cells, suggesting that the AN2 antigen plays a role in their migration. Recently, results from MALDI mass spectroscopy showed that AN2 is the mouse homologue of the rat NG2 protein. In this study, we have analyzed cells staining with AN2 antibodies during development and in the adult murine central nervous system (CNS), carried out double stainings with antibodies against NG2, and investigated the differentiation potential of cells in vitro after isolation from early postnatal brain using AN2 antibodies. AN2 and NG2 antibodies stained totally overlapping populations of cells in the CNS. AN2/NG2 expressing cells in embryonic and postnatal brain expressed the PDGF-␣-receptor and in postnatal brain exhibited electrophysiological properties typical of glial progenitor cells. Cells isolated from early postnatal brain using AN2 monoclonal antibody developed into oligodendrocytes in low serum medium or into astrocytes in the presence of fetal calf serum. In the embryonic spinal cord, cells staining with AN2 antibodies were found closely apposed to radial glial cells, suggesting that glial precursors, like neurons, may use radial glia as scaffolds for migration. GLIA 34: 213-228, 2001.
2016
Classically, the central nervous system (CNS) was considered to contain neurons and three main types of glial cells - astrocytes, oligodendrocytes, and microglia. Now, it has been clearly established that NG2-glia are a fourth glial cell type that are defined by their expression of the NG2 chondroitin sulfate proteoglycan (Cspg4). NG2-glia are also known as oligodendrocyte precursor cells (OPCs) and express the alpha receptor for platelet-derived growth factor (Pdgfra) as well as other oligodendrocyte lineage markers. NG2-glia are most numerous during CNS development when they are responsible for massive generation of oligodendrocytes, the myelin-forming cells of the CNS. A significant population of NG2-glia persist in the adult CNS, where they generate oligodendrocytes throughout life. A unique feature of NG2-glia is that they receive synaptic inputs from neurons and are able to respond rapidly to neurotransmission via their specific ion channel and receptor profiles. Moreover, syn...