Identification of a unique oligodendrocyte subpopulation in mouse brain
by Maryam Khojastehfard
Date of Examination:2017-12-04
Date of issue:2018-10-10
Advisor:Prof. Dr. Mikael Simons
Referee:Prof. Dr. Silvio Rizzoli
Referee:Prof. Dr. Henning Urlaub
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Abstract
English
Oligodendrocytes in the central nervous system (CNS) ensheath axons with myelin and are originated from migratory and proliferative progenitor cells, so-called oligodendrocytes progenitor cells (OPCs). While immunoreactivity with chondroitin sulfate proteoglycan (NG2) and platelet-derived growth factor receptor A (PDGFRα) are used to recognize OPCs, APC/CC1 positivity (adenomatous polyposis coli protein-clone CC1) represents differentiated and mature oligodendrocytes. However, a tool to distinguish newly-formed and existing oligodendrocytes is still lacking which burdens various lines of research including remyelination studies. The first aim of this study was to characterize BCAS1 as a new oligodendroglia marker which recognize newly-differentiated and early myelin-forming oligodendrocytes. We identified two different subpopulations of oligodendrocytes in developing brain, whereas only one pool continued oligodendrogenesis in adult and aged brain. By using EdU pulase-chase and transgenic reporter mice, we showed that newly-generated myelin-forming oligodendrocytes remain at a premature for relatively long time before their full maturation in adult somatosensory cortex. We also found a fraction of these premature myelin-forming cells attached to cell bodies of Tbr1-positive neurons. The second aim of this study was to address myelination at the molecular level and to define synthesis rate of myelin proteins in adult and aged mouse brain. We showed substantial increase in myelin content during adulthood which was not carried out by addition of new cells but by maturation of developmentally-born oligodendrocytes. In addition, we used biochemical characteristics of myelin proteins in order to provide a short list of true myelin proteins. So far, our knowledge about myelin composition is based on studying biochemically isolated myelin-enriched fraction. Nevertheless, a big pitfall in this approach is co-purification of any other proteins with similar floating properties to myelin. To overcome these limitations, we used different analysis to define criteria for myelin proteins and using them we provided an update into myelin proteome. Our study also provides evidences for existence of at least two different pools of myelin with different renewal rates.
Keywords: Oligodendrocyte lineage, myelin, proteomics, turnover