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| Status |
Public on Aug 03, 2020 |
| Title |
Inflammatory Signals induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Tissue regeneration is a multi-step process mediated by diverse cellular hierarchies and states that are also implicated in tissue dysfunction and pathogenesis. Here, we leveraged single-cell RNA sequencing in combination with in vivo lineage tracing and organoid models to finely map the trajectories of alveolar lineage cells during injury repair and lung regeneration. We identified a distinct AT2-lineage population, Damage-Associated Transient Progenitors (DATPs), that arises during alveolar regeneration. We found that interstitial macrophage-derived IL-1β primes a subset of AT2 cells expressing Il1r1 for conversion into DATPs via a HIF1α-mediated glycolysis pathway, which is required for mature AT1 cell differentiation. Importantly, chronic inflammation mediated by IL-1β prevents AT1 differentiation, leading to aberrant accumulation of DATPs and impaired alveolar regeneration. Together, this step-wise mapping to cell fate transitions shows how an inflammatory niche impairs alveolar regeneration by controlling stem cell fate and behavior.
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| Overall design |
For ATAC-seq of bulk (control) and Il1r1+ AT2, Tomato+ AT2 cells were isolated by FACS.
Please note that each processed .bw data was generated from both replicates and is linked to the corresponding *_1 records.
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| Contributor(s) |
Choi J, Park J, Tsagkogeorga G, Yanagita M, Koo B, Han N, Lee J |
| Citation(s) |
32750316 |
| Submission date |
Jan 31, 2020 |
| Last update date |
Nov 02, 2020 |
| Contact name |
Joo-Hyeon Lee |
| Organization name |
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge
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| Street address |
Puddicombe Way, Cambridge Biomedical Campus
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0AW |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE144553 |
Inflammatory Signals induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration |
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| Relations |
| BioProject |
PRJNA604180 |
| SRA |
SRP246322 |
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