Nishiyama Lab

Overview

NG2 cells (also known as polydendrocytes or oligodendrocyte precursor cells) represent a resident glial cell population in the mammalian central nervous system (CNS).  Their most well characterized function is to generate oligodendrocytes which produce myelin sheaths around axons and precisely regulate the timing of signal arrival.  We are interested in understanding the basic biological principles that dictate the cellular behavior NG2 cells and how NG2 cells interact with the other cellular constituents of the CNS to modulate various physiological processes. 

Current research focus

1. Molecular and cellular mechanisms that regulate the density and lineage plasticity of NG2 cells under physiological and pathological conditions.
2. How NG2 cells communicate with neurons and other cell types in the CNS.
3. The role of NG2 cells in the neural circuit, particularly in understanding whether there are functions of NG2 cells that are independent of their role as oligodendrocyte precursor cells.

We are using a wide variety of approaches to answer these questions.  Common approaches used in the lab include mouse genetics combined with immunohistochemistry, tissue culture (dissociated and organotypic), fluorescence and confocal microscopy, and biochemical and molecular biological / molecular genetic analyses.  We are also expanding our analyses to include whole animal studies such as behavioral analyses of mutant mice.  Other methods that we are incorporating into our studies include super resolution microscopy and whole genome profiling of transcripts and chromatin modifications. 

Past contributions

We have continuously made progress toward understanding the biology of NG2 cells over the past 25 years. 

1990s - We have applied immunodetection of two proteins, NG2 and platelet-derived growth factor receptor alpha (Pdgfra) to define a population of glial cells in the mammalian central nervous system (CNS). NG2 cells exist not only in the developing CNS but also are distributed uniformly throughout the mature CNS where they exhibit a complex multi-processed morphology and remain proliferative throughout life.  They are distinct from neurons, astrocytes, microglia, or mature oligodendrocytes.

2000s - There were questions about whether NG2 indeed give rise to oligodendrocytes that make myelin sheaths or whether that also serve as precursors to other cell types. To solve this question, we generated transgenic mouse lines to fate map NG2 cells at different developmental stages. NG2 cells in the postnatal brain are restricted to the oligodendrocyte lineage and those in the adult brain continue to produce myelinating oligodendrocytes. In addition, a subpopulation of NG2 cells in the prenatal CNS produce about one-third of the astrocytes in certain gray matter regions but not in the white matter.