Adaptable stem cell differentiation in the adult Drosophila intestinal epithelium
Abstract/Contents
- Abstract
- Adult organs must be able to adapt rapidly to physiological changes including injury and changes to food availability. Resident stem cells replace damaged and dying cells by dividing and differentiating, stimulated by signals emanating from the dying cells themselves. How stem cells precisely tune their differentiation to match division and death rates in real time remains a largely open question. First, I present a novel method for live imaging the adult Drosophila midgut while still intact in the living organism. With this method I am able to monitor in real time the dynamics of stem cell divisions, differentiation, and loss in the midgut. I am able to precisely measure Notch activity over time and find that a threshold level of Notch defines stem cells from their intermediate progenitors, enteroblasts. Second, I find that injury alters differentiation rates and blurs normally distinct features of stem cells, enteroblasts and terminally differentiated enterocytes. I measure rates of Notch activation and deactivation, indicators of where cells are in the differentiation process and find that both are accelerated in injured midguts. Injury raises Notch activity in mitotic stem cells beyond the enteroblast threshold and maintains Notch activity longer in maturing cells. The injury response pathway JAK-STAT appears to play a role in the acceleration of Notch deactivation kinetics and blurring between enteroblast and enterocyte characteristics, suggesting that JAK-STAT plays more of a role in regulating enterocyte maturation than enteroblast specification. Finally, I find that food consumption affects population wide Notch activity levels and excessive activation of insulin signaling might also lead to blurring between stem and enteroblast identities.
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 | Sanders, Erin Nicole |
|---|---|
| Degree supervisor | O'Brien, Lucy Erin, 1970- |
| Thesis advisor | O'Brien, Lucy Erin, 1970- |
| Thesis advisor | Fuller, Margaret T, 1951- |
| Thesis advisor | Nusse, Roel, 1950- |
| Thesis advisor | Wang, Bo, (Artificial Intelligence scientist) |
| Degree committee member | Fuller, Margaret T, 1951- |
| Degree committee member | Nusse, Roel, 1950- |
| Degree committee member | Wang, Bo, (Artificial Intelligence scientist) |
| Associated with | Stanford University, Department of Developmental Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Erin Nicole Sanders. |
|---|---|
| Note | Submitted to the Department of Developmental Biology. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/pd654gz0912 |
Access conditions
- Copyright
- © 2021 by Erin Nicole Sanders
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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