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UBC Theses and Dissertations

Gliogenesis in the adult spinal cord : spatiotemporal heterogeneity of the spinal cord central canal ependymal cells and remyelination programmes in human Multiple Sclerois Douglas, Kathryn Michelle


The developing mammalian spinal cord can generate all required cell types; in the adult, there exists a subpopulation of progenitors able to generate multiple cell types. The ependymal cell (EC) layer of the central canal (CC) of the adult spinal cord is a neural stem cell niche possessing the potential to self-renew and differentiate into astrocytes and oligodendrocytes in vivo and in vitro, and neurons in vitro. However, the differences between a developmental EC and an adult EC are not well established. Further, it is unknown whether ECs have equivalent stem/progenitor abilities, and whether certain subpopulations may be better targets for regeneration. Multiple Sclerosis (MS) is a debilitating disease characterized by areas of chronically demyelinated CNS, and an attractive target for regenerative therapy. Little is known about why endogenous regenerative programmes in MS are unsuccessful. Using in-situ hybridization (ISH) data from the Allen Spinal Cord Atlas and immunofluorescent detection of antigen in mice, we revealed temporal and spatial segmentation of ECs expressing distinct groups of genes. The ages analyzed (postnatal day 4 and 56) are relevant to the mechanisms of neurogenesis and gliogenesis, as the spinal cord is capable of regaining greater functionality following injury at P4 than at P56. Gene ontology analysis suggests different regions of the CC may contribute in different ways to spinal cord repair. Furthermore, we found the EC niche experiences altered levels of proliferation after two different types of insult, SCI and demyelinating injury in mice. We then used MS spinal cord to test what extent such repair from demyelination takes place. We found that remyelination occurred, but was inadequate and highly variable both between and within patients. Abnormal myelinating cells of a unique phenotype were found in the CNS and PNS; the extent and prevalence of peripheral involvement has not been previously reported. Further work is needed to determine whether the human EC layer could be targeted to enhance remyelination. Overall, these results reveal novel cell phenotypes engaged in repair in mouse and human spinal cord that may serve a basis for future therapeutic intervention.

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