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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 16, 2024 |
| Title |
Single-cell division tracing and transcriptomics reveal cell types and differentiation paths in the regenerating lung |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of therapeutic approaches for lung diseases. We combine mouse models allowing diphtheria toxin-mediated damage of specific epithelial cell types and parallel GFP-labeling of functionally dividing cells with single-cell transcriptomics to characterize the regeneration of the distal lung. We uncover cell types, including Krt13+ basal and Krt15+ club cells, detect an intermediate cell state between basal and goblet cells, reveal goblet cells as actively dividing progenitor cells, and provide evidence that adventitial fibroblasts act as supporting cells in epithelial regeneration. We also show that diphtheria toxin-expressing cells can persist in the lung, express specific inflammatory factors, and transcriptionally resemble a previously undescribed population in the lungs of COVID-19 patients. Our study provides a comprehensive single-cell atlas of the distal lung that characterizes early transcriptional and cellular responses to concise epithelial injury, encompassing proliferation, differentiation, and cell-to-cell interactions.
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| Overall design |
Epithelial and/or mesenchymal cells were sorted from uninjured mouse lungs or from mouse lungs were club or AT2 and club cells were killed via DTA expression. Dividing cells and rare cell types were enriched during sorting.
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| Web link |
https://www.nature.com/articles/s41467-024-46469-4
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| Contributor(s) |
Martins LR, Sieverling L, Michelhans M, Erkut C, Velten L |
| Citation(s) |
38472236 |
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| Submission date |
Jan 26, 2023 |
| Last update date |
Sep 09, 2024 |
| Contact name |
Cihan Erkut |
| E-mail(s) |
cihan.erkut@nct-heidelberg.de
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| Organization name |
German Cancer Research Center
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| Department |
Applied Functional Genomics
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| Street address |
Im Neuenheimer Feld 581
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| City |
Heidelberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
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| Platforms (2) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (16)
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| GSM7011597 |
Dividing epithelial and mesenchymal cells, SRC mice, injured lung, day2 |
| GSM7011598 |
Dividing epithelial and mesenchymal cells, SRC mice, injured lung, day3 |
| GSM7011599 |
Mesenchymal cells, SRC mice, uninjured lung, day0 |
| GSM7011600 |
Mesenchymal cells, SRC mice, injured lung, day2 |
| GSM7011601 |
Mesenchymal cells, SRC mice, injured lung, day3 |
| GSM7011602 |
Dividing mesenchymal cells, SRC mice, injured lung, day2 |
| GSM7011603 |
Dividing mesenchymal cells, SRC mice, injured lung, day3 |
| GSM7011604 |
Epithelial cells AT2-depleted, SRC mice, uninjured lung, day0 |
| GSM7011605 |
Epithelial cells AT2-depleted and dividing epithelial cells, SRC mice, injured lung, day2 |
| GSM7011606 |
Epithelial cells AT2-depleted and dividing epithelial cells, SRC mice, injured lung, day3 |
| GSM7011607 |
Epithelial cells AT2-depleted and dividing epithelial cells, SRC mice, injured lung, day4 |
| GSM7011608 |
Epithelial cells AT2- and ciliated-depleted and dividing epithelial cells, SRC mice, uninjured lung, day0 |
| GSM7011609 |
Epithelial cells AT2- and ciliated-depleted and dividing epithelial cells, SRC mice, injured lung, day2 |
| GSM7011610 |
Epithelial cells AT2- and ciliated-depleted and dividing epithelial cells, SfSRC mice, uninjured lung, day0 |
| GSM7011611 |
Epithelial cells AT2- and ciliated-depleted and dividing epithelial cells, SfSRC mice, injured lung, day2 |
| GSM7011612 |
Epithelial cells AT2- and ciliated-depleted and dividing epithelial cells, SfSRC mice, injured lung, day3 |
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| Relations |
| BioProject |
PRJNA929542 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE223816_RAW.tar |
657.6 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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