The role of TET1-mediated 5hmC in skeletal development and disease
Abstract/Contents
- Abstract
- Cartilage, a mostly avascular tissue, is composed primarily of extracellular matrix proteins (ECM), in which resident cells, called chondrocytes, are embedded. Despite our knowledge about the biomechanical properties of cartilage, we still know relatively little about the identities of the chondrocytes embedded in the ECM matrix, and how they change with aging, injury, and chronic joint disease. The work described within this dissertation touches on two aspects of the molecular identities of these resident cells. First, in chapter 2, I describe work using cytometry by time-of-flight to characterize subpopulations of chondrocytes in human cartilage, and how these populations change with disease. I identify two new subpopulations, termed the Inflammation-Amplifying and Inflammation-Dampening cells, and demonstrate that drug modulations to their activities can alter disease progression. In chapters 3 and 4, the work switches to considering the epigenetic code that establishes cell identity. This work focuses on a chemical modification to the cytosine base, known as 5-hydroxymethylcytosine (or 5hmC), which marks the gene bodies of actively transcribed genes. In Chapter 3, I look at the role of this modification during cartilage development, and specifically how it primes the chromatin landscape for the transcription factor SOX9, allowing chondrocyte-specific genes to be expressed. In Chapter 4, I look at the role of 5hmc in disease progression of osteoarthritis
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Grandi, Fiorella Carla |
|---|---|
| Degree supervisor | Bhutani, Nidhi |
| Thesis advisor | Bhutani, Nidhi |
| Thesis advisor | Chan, Charles K. F. (Charles Kwok Fai), 1975-2024 |
| Thesis advisor | Wang, Kevin C. (Kevin Chun-Kai) |
| Thesis advisor | Wu, Joy |
| Thesis advisor | Van Rechem, Capucine |
| Degree committee member | Chan, Charles K. F. (Charles Kwok Fai), 1975-2024 |
| Degree committee member | Wang, Kevin C. (Kevin Chun-Kai) |
| Degree committee member | Wu, Joy |
| Degree committee member | Van Rechem, Capucine |
| Associated with | Stanford University, Cancer Biology Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Fiorella Carla Grandi |
|---|---|
| Note | Submitted to the Cancer Biology Program |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | https://purl.stanford.edu/vd539zk3673 |
Access conditions
- Copyright
- © 2020 by Fiorella Carla Grandi
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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