Oligondendrocyte progenitors and their role in adult neural cell genesis.
Doctoral thesis, UCL (University College London).
Oligodendrocyte progenitors (OLPs) are widely distributed throughout the embryonic and adult central nervous system (CNS). They are the primary, possibly the only source of oligodendrocytes in the developing CNS and in the repair of demyelinated lesions, but it is unclear whether they continue to generate myelinating oligodendrocytes or any other cells in the normal healthy adult. A transgenic mouse line, Pdgfra-CreERT2, allowed temporally-controlled, permanent activation of YFP expression in PDGFRa-expressing OLPs and their differentiated progeny in the Rosa26-YFP reporter background. In vivo BrdU labelling and fate mapping of YFP-positive cells revealed that, in the corpus callosum, approximately half of the OLPs were dividing with a cell cycle time of approximately 8 days. Half of the daughter cells differentiated into myelinating oligodendrocytes, the others remained undifferentiated to maintain the OLP population. In the cortex, the majority of differentiated cells were SOX10+ non-myelinating oligodendrocyte-lineage cells of unknown function. In addition, YFP-labelled projection neurons accumulated in the piriform cortex (primary olfactory cortex). YFP-labelled astrocytes were not found anywhere in the forebrain. In collaboration with RMJ Franklin and colleagues (University of Cambridge) the fates of OLPs during repair of gliotoxin-induced demyelinated spinal cord lesions were investigated. In the lesions, OLPs generated mainly remyelinating oligodendrocytes and Schwann cells as well as a few astrocytes. Taken together, my in vivo Cre/lox fate-mapping studies showed that OLPs can differentiate into myelinating oligodendrocytes, non-myelinating oligodendrocytelineage cells, cortical projection neurons and - during remyelination - Schwann cells and astrocytes. Thus, OLPs possess multipotential stem cell-like properties in the adult mouse CNS.
|Title:||Oligondendrocyte progenitors and their role in adult neural cell genesis|
|Additional information:||Authorisation for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Wolfson Inst for Biomedical Research|
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