An analysis of stem cell trajectories and their molecular determinants
Abstract/Contents
- Abstract
- The stem cell is the central unit of generation and regeneration throughout life in all complex multicellular organisms, including humans. A detailed understanding of stem cells and their properties is required to unlock the vast promises of 21st century biology across topics ranging from regenerative medicine to gene editing to reproductive medicine. Starting from the discovery of hematopoietic stem cells in 1988, stem cells have been identified in most developing and adult tissues. Of particular interest to regenerative medicine are tissue-specific stem cells. They exist throughout the organism's life and they can thus in theory be isolated from and their abilities be harnessed for most adult patients. Two central questions have to be answered for every adult tissue of interest: 1) what is the identity of the stem cell in the tissue; and 2) how are the tissue's stem cells properties regulated; specifically, how are they maintained throughout life and what molecular signals induce their differentiation into any of the cell types they can generate? The first question is therefore of interest to the many remaining tissues of which the description of the cellular hierarchy is incomplete. This includes many cancers, which tend to display slightly altered hierarchical relationships compared to their normal tissue equivalents. A notable exception is the hematopoietic stem cell, which is understood in significantly more detail than any other adult stem cell. The hematopoietic system is thus a prime candidate to study the second question, both regarding general themes of stem cell biology as well as the development of methods of analysis that can eventually be applied to other stem cell systems. In this dissertation, I examine the utility of gene expression and chromatin accessibility in two contexts: 1) globally to identify stem cells, and 2) regarding specific genes to understand behavioral changes of stem cells. In the first part of this dissertation I address the question of stem cell identity. I first discuss how to identify stem cells and tissue hierarchies in a data-driven manner, starting from scRNA-seq data. Next, I show the application of these principles to the human liver. The second part of this dissertation concerns stem cell behavior regarding differentiation in the example of the hematopoietic system. In Chapter 4 I assess stem cell heterogeneity and its influence on functional outcomes of differentiation. Finally, I discuss preliminary evidence for a novel feedback mechanism from the peripheral lymphoid lineage to the hematopoietic stem cell in Chapter 5.
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 | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Wesche, Daniel Jonathan |
|---|---|
| Degree supervisor | Weissman, Irving L |
| Thesis advisor | Weissman, Irving L |
| Thesis advisor | Newman, Aaron, (Biomedical data scientist) |
| Thesis advisor | Wysocka, Joanna, Ph. D. |
| Degree committee member | Newman, Aaron, (Biomedical data scientist) |
| Degree committee member | Wysocka, Joanna, Ph. D. |
| Associated with | Stanford University, Program in Stem Cell Biology and Regenerative Medicine |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Daniel Jonathan Wesche. |
|---|---|
| Note | Submitted to the Program in Stem Cell Biology and Regenerative Medicine. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/wm483jg6571 |
Access conditions
- Copyright
- © 2021 by Daniel Jonathan Wesche
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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