Mapping cellular and molecular programs for ultra-rapid alveolar epithelial regeneration
Abstract/Contents
- Abstract
- With each breath gasses are exchanged across extraordinarily thin and expansive alveolar type I (AT1) cells adapted for diffusion. Cuboidal alveolar type II (AT2) cells are interspersed and act as stem cells. Even transient disruption of this delicate monolayer epithelium can result in capillary leak and respiratory failure. Here, we exploited genetic and chemical methods to ablate AT1 cells and dissected the earliest steps in alveolar regeneration. This uncovered ultra-rapid AT2-to-AT1 cell transdifferentiation that enabled near-continuous maintenance of the epithelial barrier. Proliferation subsequently restored AT2 cells in two phases, immediate mitosis of binucleated AT2 cells followed by replication of mononucleated AT2 cells. EGFR regulated both M phase entry of binucleated cells and S phase entry of mononucleated cells in a Wnt-dependent manner. Repeated cycles of AT1 cell death did not compromise the barrier, but rather elicited epithelial hyperplasia that fortified the epithelium during ongoing injury then spontaneously resolved. We propose a two-step mechanism in which regeneration of the epithelial barrier precedes stem cell proliferation.
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 | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Guild, Joshua Daniel |
|---|---|
| Degree supervisor | Desai, Tushar |
| Thesis advisor | Desai, Tushar |
| Thesis advisor | Beachy, Philip Arden |
| Thesis advisor | Nicolls, Mark |
| Thesis advisor | Nusse, Roel, 1950- |
| Thesis advisor | Utz, PJ |
| Degree committee member | Beachy, Philip Arden |
| Degree committee member | Nicolls, Mark |
| Degree committee member | Nusse, Roel, 1950- |
| Degree committee member | Utz, PJ |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Program in Stem Cell Biology and Regenerative Medicine |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Joshua Daniel Guild. |
|---|---|
| Note | Submitted to the Program in Stem Cell Biology and Regenerative Medicine. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/pw224jt9579 |
Access conditions
- Copyright
- © 2023 by Joshua Daniel Guild
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...