Abstract
SummaryTwo populations of oligodendrogenic progenitors co-exist within the corpus callosum (CC) of the adult mouse. Local, parenchymal oligodendrocyte progenitor cells (pOPCs) and progenitors generated in the subependymal zone (SEZ) cytogenic niche. pOPCs are committed perinatally and retain their numbers through self-renewing divisions, while SEZ-derived cells are relatively “young,” being constantly born from neural stem cells. We compared the behavior of these populations, labeling SEZ-derived cells using hGFAP:CreErt2 mice, within the homeostatic and regenerating CC of the young-adult and aging brain. We found that SEZ-derived oligodendroglial progenitors have limited self-renewing potential and are therefore not bona fide OPCs but rather “oligodendroblasts” more similar to the neuroblasts of the neurogenic output of the SEZ. In the aged CC their mitotic activity is much reduced, although they still act as a “fast-response element” to focal demyelination. In contrast to pOPCs, they fail to generate mature myelinating oligodendrocytes at all ages studied.
Highlights
Myelination of the CNS of mice occurs mainly within the first 4 post-natal weeks when oligodendrocyte progenitor cells (OPCs) differentiate into myelin-forming oligodendrocytes
SezOPCs are Labeled in hGFAP:CreERT2 x Rosa26:EYFP Mice Adult Neural stem cells (NSCs) express glial acidic fibrillary protein (GFAP) (Doetsch et al, 1999), the expression of which decreases abruptly in downstream progenitors, such as neuroblasts (Pastrana et al, 2009)
We used hGFAP:CreERT2 x ROSA26:EYFP double transgenic mice (Hirrlinger et al, 2006)
Summary
Myelination of the CNS of mice occurs mainly within the first 4 post-natal weeks when oligodendrocyte progenitor cells (OPCs) differentiate into myelin-forming oligodendrocytes. After this period, adult OPCs of divergent developmental origins remain scattered throughout the CNS parenchyma (Crawford et al, 2016). SEZ-derived and parenchymal OPCs (sezOPCs and pOPCs, respectively) differ in their cellular origin and in their cellular age, since pOPCs are committed during the early post-natal period and retain their numbers through self-renewing divisions, while new sezOPCs are constantly born within the microenvironment of the niche. Based on previous work suggesting that adult pOPCs behave differently to perinatal OPCs (Windrem et al, 2004; Wolswijk and Noble, 1989), and that a fraction of aging pOPCs expresses markers of senescence (Kujuro et al, 2010), we compared the behavior of sezOPCs and pOPCs, in both homeostatic and regenerating tissue in the young and aged brain
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