Origin of Oligodendrocytes in the Subventricular Zone of the Adult Brain

Harvard University, Cambridge, Massachusetts, United States
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 08/2006; 26(30):7907-18. DOI: 10.1523/JNEUROSCI.1299-06.2006
Source: PubMed


Glial fibrillary acidic protein (GFAP)-positive astrocytes (type B cells) in the subventricular zone (SVZ) generate large numbers of new neurons in the adult brain. SVZ stem cells can also generate oligodendrocytes in vitro, but it is not known whether these adult primary progenitors generate oligodendrocytes in vivo. Myelin repair and oligodendrocyte formation in the adult brain is instead associated with glial-restricted progenitors cells, known as oligodendrocyte progenitor cells (OPCs). Here we show that type B cells also generate a small number of nonmyelinating NG2-positive OPCs and mature myelinating oligodendrocytes. Some type B cells and a small subpopulation of actively dividing type C (transit-amplifying) cells expressed oligodendrocyte lineage transcription factor 2 (Olig2), suggesting that oligodendrocyte differentiation in the SVZ begins early in the lineage. Olig2-positive, polysialylated neural cell adhesion molecule-positive, PDGF receptor alpha-positive, and beta-tubulin-negative cells originating in the SVZ migrated into corpus callosum, striatum, and fimbria fornix to differentiate into the NG2-positive nonmyelinating and mature myelinating oligodendrocytes. Furthermore, primary clonal cultures of type B cells gave rise to oligodendrocytes alone or oligodendrocytes and neurons. Importantly, the number of oligodendrocytes derived from type B cells in vivo increased fourfold after a demyelinating lesion in corpus callosum, indicating that SVZ astrocytes participate in myelin repair in the adult brain. Our work identifies SVZ type B cells as progenitors of oligodendrocytes in normal and injured adult brain.

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    • "About 10,000 new neurons are generated daily in the mouse SVZ (Ponti et al., 2013), half of which will die before functional integration (Petreanu and Alvarez-Buylla, 2002; Winner et al., 2002), the survivors differentiating into subsets of olfactory bulb interneurons (Obernier et al., 2014). Only small numbers of oligodendrocytes are generated in vivo (Menn et al., 2006), whereas in culture, after expansion of the NSC population, most of the progeny acquires aglial (mainly astrocytic) fate, with only 10–20% of neurons (Gritti et al., 2009). In the SGZ, new neurons arise from two populations of primitive cells (radial – NSCs – and horizontal, slowly dividing cells; Ming and Song, 2011). "
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    • "Lim and Alvarez-Buylla first described the close interaction of astrocytes and neural precursor cells in the SVZ niche (Lim and Alvarez-Buylla, 1999), which paralleled the discovery by the same group that the precursor cells actually have astrocyte-like properties themselves (Doetsch et al., 1999), also in the human brain (Sanai et al., 2004). That group also highlighted the lineage-relationship between astrocyte-like precursor cells and the generation of oligodendrocytes in the SVZ (Menn et al., 2006). Whereas in the SGZ a small number of new oligodendrocytes is found (Kempermann et al., 2003), these originate from a different set of precursor cells than the neurons and astrocytes . "
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    • "to migrate to the lesion area upon CNS disease (Goings et al, 2004; Sundholm-Peters et al, 2005; Menn et al, 2006; Benner et al, 2013) (Fig 3A). Our results revealed that BrdU+Thbs4+ SVZ-generated astrocytes as well as BrdU+Olig2+ C cells co-express GFAP in the lesion area at 10 days after SWI and therefore contribute to the cortical lesion astrocyte population and are the potential source for Id3-regulated NSPC differentiation into astrocytes after injury (Fig 3A and B). "
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