Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity

Abstract

NG2 cells (also known as polydendrocytes) are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes and microglia. They can be identified by the expression of the proteoglycan NG2, have a highly branched morphology and are distributed throughout the grey and white matter. They differentiate into oligodendrocytes in vitro and have often been equated with oligodendrocyte precursor cells. However, whether polydendrocytes are multipotential cells that can give rise to neurons and astrocytes as well as oligodendrocytes is now highly debated. Furthermore, electrophysiological studies indicate that polydendrocytes receive synaptic input from neurons, suggesting that they are integrated in the neural network. This Review highlights recent findings and unresolved questions related to the lineage and function of polydendrocytes in the CNS.

Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain

“…New examples of cell genesis, involving both neurogenesis and gliogenesis, have been shown to occur in the so-called nonneurogenic regions of the mammalian CNS (Table 1). Local, parenchymal progenitors that retain some proliferative capacity have been detected in most regions of the mature CNS (Horner et al 2000;Dayer et al 2005;Kokoeva et al 2005;Luzzati et al 2006;Ponti et al 2008;reviewed in Butt et al 2005;Nishiyama et al 2009;Migaud et al 2010;Bonfanti and Peretto 2011), suggesting that structural plasticity involving de novo neural cell genesis could be more widespread than previously thought. Apart from their temporal persistence (some of them represent examples of delayed developmental neurogenesis, which persist postnatally; see below), neurogliogenic processes vary as to their regional localization, origin, and final outcome.…”

“…To further complicate the picture is the existence of glial progenitors retaining proliferative capacity in wide areas of the mature CNS (reviewed in Dawson et al 2000;Butt et al 2005;Nishiyama et al 2009;Trotter et al 2010). The largest class of these cells express NG2 (Horner et al 2000) and are often referred to simply as NG2 cells.…”

Silencing or knocking out the Na+/Ca2+ exchanger-3 (NCX3) impairs oligodendrocyte differentiation

“…1 Although many OPCs differentiate into mature myelinating oligodendrocytes during the early and much later stages of human brain development, a considerable number of them do persist in the adult brain, and may provide a source of new oligodendrocytes, as well as protoplasmic astrocytes and neurons. 2,3 Because of their apparent stem-like characteristics, adult OPCs have recently gained much attention, for they are regarded as a potential reservoir of cells capable of self-renewal, differentiation, and re-myelination after CNS injury. 4 Thus, understanding how oligodendrocyte development proceeds and what factors govern the differentiation fate of OPCs is crucial to discover new effective therapeutic targets for de-myelinating diseases such as multiple sclerosis (MS).…”

Oligodendrocyte Fate after Spinal Cord Injury

“…These OL progenitors cells (commonly called OPCs or polydendrocytes) are present throughout the adult gray and white matter, and respond to demyelination by proliferating and migrating into the demyelinated zone [53][54][55][56]. Adult OPCs, typically identified by Nerve/glial antigen 2 (NG2) or Platelet derived growth factor receptor (PDGFRα) expression, are thought to be a heterogeneous cell population, only some of which function as OPCs (for review, see Nishiyama et al [57] and Trotter et al [58]). …”