Alveolar stem cells and niches in aging, injury and evolution
Abstract/Contents
- Abstract
- The lung is the primary organ of respiration and the site of diseases that cause 7 million deaths annually. Although relatively understudied at the turn of the century, the field of lung stem cell biology is experiencing a renaissance due to advances in the ability to monitor and genetically mark and manipulate cells in mice. This dissertation focuses on two major topics in the field. In the first part, I focus on the identification of the alveolar stem, its niche and the signals regulating alveolar stem cell identity. I show that alveolar stem cells display active Wnt signaling, which imparts upon them the ability to proliferate and inhibits their transdifferentiation. Wnt signaling is activated by a juxtacrine signal from a single, neighboring fibroblast. I also describe how alveolar stem cells react to injury and the increased need for regeneration. I show that quiescent AT2 cells are recruited as emergency stem cells during injury through a transient autocrine source of Wnt signaling. I then describe the probing by single cell transcriptomics of the molecular underpinnings of alveolar stem cells and how they differ from other alveolar epithelial cells. Last, I describe a cellular transplantation assay developed for future study of these cells. The second part of my dissertation focuses on creating molecular cell atlases of mouse and human lungs. As a member of the Tabula Muris consortium, I led a team that captured lung tissues and analyzed data for the lung, spleen and kidney. I then describe my collaborative effort to create a molecular cell atlas of the human lung by single cell RNA sequencing (scRNAseq), for which we sequenced > 70,000 cells and molecularly characterized 58 molecular cell types including 14 novel populations. I then use these data to analyze mammalian lung evolution at single cell resolution. Finally, I describe my efforts to discover the molecular program responsible for the unique flat morphology of AT1 cells, which comprise one side of the gas exchange surface and enables efficient exchange of gases.
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 | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Nabhan, Ahmad N | |
|---|---|---|
| Degree supervisor | Krasnow, Mark, 1956- | |
| Thesis advisor | Krasnow, Mark, 1956- | |
| Thesis advisor | Artandi, Steven E | |
| Thesis advisor | Desai, Tushar | |
| Thesis advisor | Rohatgi, Rajat | |
| Degree committee member | Artandi, Steven E | |
| Degree committee member | Desai, Tushar | |
| Degree committee member | Rohatgi, Rajat | |
| Associated with | Stanford University, Department of Biochemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Ahmad N. Nabhan. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Ahmad N Nabhan
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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