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| Status |
Public on Jun 08, 2022 |
| Title |
Klf5 promotes alveolar epithelial type 1 cell lineage commitment during lung development and regeneration |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Alveolar epithelial cell fate decisions drive lung development and regeneration. Using transcriptomic and epigenetic profiling coupled with genetic mouse and organoid models, we identified Klf5 as a critical regulator of alveolar epithelial cell fate across the lifespan. During prenatal lung development and alveologenesis, Klf5 enforces alveolar epithelial type 1 (AT1) cell lineage fidelity. While it is dispensable for both adult AT1 and alveolar epithelial type 2 (AT2) cell homeostasis, Klf5 regulates AT2 cell plasticity after injury. Klf5 represses AT2 cell proliferation and enhances AT2-AT1 cell differentiation in a spatially restricted manner in both infectious and non-infectious models of acute respiratory distress syndrome. Moreover, ex vivo organoid assays reveal that Klf5 modulates AT2 cell fate decisions through reducing AT2 cell sensitivity to inflammatory signaling. These data highlight a major transcriptional regulator of AT1 cell lineage commitment and of the AT2 cell response to inflammatory crosstalk during lung regeneration.
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| Overall design |
Adult control and Klf5-deficient mouse AT2 cells were isolated 3 days after hyperoxic lung injury.
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| Contributor(s) |
Liberti DC, Morley MP, Morrisey EE |
| Citation(s) |
35803279 |
| |
| Submission date |
Dec 10, 2021 |
| Last update date |
Sep 07, 2022 |
| Contact name |
Michael Patrick Morley |
| E-mail(s) |
[email protected]
|
| Phone |
215-898-2026
|
| Organization name |
Perelman School of Medicine at the University of Pennsylvania
|
| Department |
Penn Cardiovascular Institute
|
| Street address |
3400 Civic Center Blvd, Bldg 421
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA787949 |
| SRA |
SRP350278 |
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