Rejuvenation of CNS Progenitors via Partial Reprogramming

Adult stem cells become less efficient at maintaining tissue integrity and repairing tissue damage with age. Oligodendrocyte progenitor cells (OPCs) are the largest population of stem cells in the adult CNS and give rise to oligodendrocytes. OPCs play a critical role in myelin regeneration (remyelination), but, like all stem cells, their regenerative capacity declines with age. OPCs progressively fail to differentiate into mature oligodendrocytes following a demyelinating insult with age, and this failure plays a key role in the progression of prominent neurodegenerative and demyelinating diseases, such as Alzheimer’s disease and multiple sclerosis. I have optimised an existing system for isolating OPCs from aged rats to assess rejuvenation strategies in vitro, designed novel OPC-specific rAAV vectors to manipulate gene expression in these cells, and used these tools to show that overexpression of MYBL2 in aged OPCs increases their differentiation capacity in vitro. My work adds to a growing body of literature showing that overexpression of specific factors in specific tissues is sufficient to rejuvenate their resident aged cells.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

Sidney Sussex College

Year dc:date.issued

2022

Author dc:creator

• Sharma, Amar

Advisor dc:contributor.advisor

• Franklin, Robin

• Rejuvenation
• Partial Reprogramming
• OPC
• Oligodendrocyte
• AAV
• Gene therapy
• Stem Cells

Licence

• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.90176

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/342762