Studies of skeletal muscle satellite cell death and renewal
Abstract/Contents
- Abstract
- Skeletal muscle is an abundant tissue, accounting for 42% of the body mass of the average adult male human, and is required to generate the force necessary for movement and posture. The regeneration of skeletal muscle tissue in mammals is accomplished by a rare population of muscle-resident adult stem cells known as satellite cells. These satellite cells primarily reside in a dormant state and are prompted to carry-out their regenerative function by an injury to the neighboring muscle tissue. Atrophy and impaired regeneration of skeletal muscle are significant comorbidities of aging and chronic illness. This dissertation describes and interprets studies of skeletal muscle stem cell biology with particular attention paid to molecular mechanisms that influence stem cell-fate during regeneration in healthy and diseased contexts. The hypothesis that changes in stem cell regenerative potential underlie the poor tissue repair observed in aged animals is explored through comparisons of young and old cells. These studies identify a unique mitotic cell death phenomenon that occurs specifically within old cells as a consequence of age-associated changes in the satellite cell environment. In additional analyses, broad characterizations of gene expression in human satellite cells are leveraged to develop pharmacologic methods for controlling cell-fate to enhance the regenerative potential of purified cells. These analyses also provide insight into human-specific mechanisms of satellite cell-mediated myogenesis. The final series of studies uses satellite cells as a model system to examine cell-fate determination during stem cell divisions that give rise to daughter cells with divergent fates. These so-called asymmetric cell divisions are characterized specifically in terms of the unique patterns of chromosome segregation observed to coincide with regulation of muscle stem cell fate.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2015 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Charville, Gregory William | |
|---|---|---|
| Associated with | Stanford University, Department of Developmental Biology. | |
| Primary advisor | Rando, Thomas A | |
| Thesis advisor | Rando, Thomas A | |
| Thesis advisor | Kim, Seung K | |
| Thesis advisor | Nusse, Roel, 1950- | |
| Advisor | Kim, Seung K | |
| Advisor | Nusse, Roel, 1950- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Gregory William Charville. |
|---|---|
| Note | Submitted to the Department of Developmental Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Gregory William Charville
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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