Proteostatic mechanisms and degree of transcriptional change with age in different neural stem cell populations
Abstract/Contents
- Abstract
- The stem cell pool of most organs contains quiescent and actively dividing (activated) populations. These populations face different challenges over the course of life, raising the question of whether they maintain homeostasis differently and age in different ways. In this work, I perform transcriptomic profiling on multiple populations of the brain's regenerative neural stem cell (NSC) pool from young and old mice to gain an unbiased overview of their differential homeostatic properties and their changes with age. Interestingly, I find that quiescent and activated NSC populations differ in their degree of transcriptome-wide change with age and express different transcriptional signatures for the three primary branches of protein homeostasis (proteostasis)—the proteasome, the lysosome, and molecular chaperones. Additionally, aspects of these divergent modes of proteostasis can be generalized to other organs' stem cells. I functionally validate that quiescent and activated NSC populations differ in their regulation of multiple branches of proteostasis. Intriguingly, the populations with less active proteasomes and lysosomes also have higher levels of protein aggregates and undergo a greater degree of transcriptional change with age. Additionally, I find that the genes most changed with age in each cell type are the genes that constitute that cell type's signature with regard to quiescence and activation. Together, these findings highlight novel differences in the proteostatic strategies used by different stem cell populations that could potentially contribute to their differential aging.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Leeman, Dena S |
|---|---|
| Associated with | Stanford University, Cancer Biology Program. |
| Primary advisor | Brunet, Anne, 1972- |
| Thesis advisor | Brunet, Anne, 1972- |
| Thesis advisor | Palmer, Theo |
| Thesis advisor | Winslow, Monte |
| Advisor | Palmer, Theo |
| Advisor | Winslow, Monte |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Dena S. Leeman. |
|---|---|
| Note | Submitted to the Program in Cancer Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Dena Simona Leeman
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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