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| Status |
Public on Apr 16, 2024 |
| Title |
CEBPA restricts alveolar type 2 cell plasticity during development and injury-repair [scATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Cell plasticity theoretically extends to all possible cell types, but naturally decreases as cells differentiate, whereas injury-repair re-engages the developmental plasticity. Here we show that the lung alveolar type 2 (AT2)-specific transcription factor (TF), CEBPA, restricts AT2 cell plasticity in the mouse lung. AT2 cells undergo transcriptional and epigenetic maturation postnatally. Without CEBPA, both neonatal and mature AT2 cells reduce the AT2 program, but only the former reactivate the SOX9 progenitor program. Sendai virus infection bestows mature AT2 cells with neonatal plasticity where Cebpa mutant, but not wild type, AT2 cells express SOX9, as well as more readily proliferate and form KRT8/CLDN4+ transitional cells. CEBPA promotes the AT2 program by recruiting the lung lineage TF NKX2-1. The temporal change in CEBPA-dependent plasticity reflects AT2 cell developmental history. The ontogeny of AT2 cell plasticity and its transcriptional and epigenetic mechanisms have implications in lung regeneration and cancer.
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| Overall design |
FACS-purified lung epithelial, immune, endothelial, and mesenchymal cells were processed using the 3′ Library and Gel Bead Kit following the manufacturer’s users guide (v2 rev D) on the Chromium Single-Cell Gene Expression Solution Platform (10X Genomics).
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/38755149/
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| Contributor(s) |
Hassan D, Chen J |
| Citation(s) |
38755149 |
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| Submission date |
Apr 16, 2024 |
| Last update date |
May 21, 2024 |
| Contact name |
Dalia Hassan |
| E-mail(s) |
dhassan@mdanderson.org
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| Phone |
3467146254
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| Organization name |
MD Anderson Cancer Center
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| Department |
Pulmonary Medicine
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| Lab |
Jichao Chen
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| Street address |
6565 MD Anderson Blvd, Z9.4040, Z9.4040
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| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1100986 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE264098_RAW.tar |
4.9 Gb |
(http)(custom) |
TAR (of BROADPEAK, BW, RDS) |
SRA Run Selector |
| Raw data are available in SRA |
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